Available online on 15.07.2024 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright   © 2024 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                                         Review Article

Platinum nanoparticles as delivery system in combating various diseases

Ardhendu Kumar Mandal 

Central Instrumentation Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India

 

 

Introduction

Infectious diseases and cancer including tumors are caused by the exposure of pathogens, toxicants or carcinogens. In general, the antioxidant and the immune (innate and acquired) body defense systems have the ability to prevent the biological system from the initiation of disease and the subsequent development of infection ¹. However, pathogens, contagious and virulent agents or toxicants are transmitted into the host body system and overpower the systemic defense mechanisms to initiate site-infections followed by their multiplications and / or host-cells-injuries, genetic mutations or DNA damages leading to the development and progression of diseases, cancer, metastatic cancer or tumors ^2-5. Conventional chemotherapy produces improper dose application-related drug resistance and high drug dosage-oriented cytotoxicity to healthy cells aggravating the disease condition of the patients ⁶. Moreover, chemotherapeutics also face various constraints such as their insolubility, toxicity, non-specificity, low bio-stability, biological barriers and low therapeutic indexes that implicate sufferings further to patients ⁷. To overcome the obstacles, nanotechnology based metallic PtNPs have gained attention owing to their specific shape, size, large surface area, lower cytotoxicity, easy surface functionalization, electro-catalyzing capability (oxidation, hydrogenation and dehydrogenation), resistancy to corrosion and chemical attacks, chemical stability and resistancy to ionization, photothermal, photoacoustic and surface plasmon resonance (SPR) -related optical characteristics owing to the enhanced interactions of light and the free electrons on the nearby molecules of the metallic NPs’ surfaces causing collective oscillations of the conduction band electrons^8-15. PtNPs may penetrate cell membrane causing leakage of membrane and interact with intracellular components leading to DNA or cellular damage through the release of platinum ions ^16,17. Owing to the high ratio of electrons to particle surface, PtNPs may regulate oxidative stress and induct the apoptotic death of cancer cells via DNA damages and inhibiting their replications ^18-22. PtNPs may function as potent and stable mimetics of superoxide dismutase and catalase to attenuate oxidative stress-induced inflammation and / or injury in the biological system through the scavenging of ROS ^23-25,20. PtNPs may be modified with various surface coating materials such as polymers (poly-lactide-co-glycolide, poly-L-lactic acid, poly-ethylene glycol,  polyvinyl alcohol, chitosan and alginate) with drugs to get a long circulation half-life and controlled drug release for the accumulation in tumor region/s implicating their higher biocompatibility and reverse drug resistance activities through passive targeting ^26-34. Moreover, they may be conjugated with antibodies, nucleic acids, peptides, targeting ligands, aptamers and drugs to provide the effective active targeting therapy ^35-40. Hybrid bimetallic porous NPs such as Au-Pt, Fe-Pt NPs conjugated with drugs and /or ligands may exhibit their higher optical, magnetic and / or infrared radiation-based anticancer efficacy through chemo-photothermal, imaging guided photoacoustic or hyperthermal therapy ^41-54. This review elucidates chiefly the PtNPs as potent drug delivery system against various diseases on the basis of their therapeutic biological efficacies.

 

Synthesis of platinum nanoparticles and their hybrid forms

The shape and size of the chemically synthesized PtNPs may vary depending on the reaction temperature, the appropriate selection of solvents (such as ethylene glycol), concentration of precursors (such as H₂PtCl₆), and the type and concentration of stabilizing (such as polyvinyl pyrrolidone (PVP)) and reducing agents (such as sodium hydroxide) ⁵⁵. The chemical reduction is chiefly utilized for colloidal NPs-production in which chemical agents reduce the metallic ions to form metallic NPs. The chemical agents such as sodium borohydride (NaBH₄), potassium bitartrate (KC₄H₅O₆), ascorbate, trisodium citrate dehydrate (Na₃C₆H₉O₉), methoxy polyethylene glycol (CH₃O(CH₂CH₂O)nH), and elemental hydrogen are utilized for the reduction processes. The spherical PtNPs with small sizes (1-2 and 2-3 nm) may be obtained from H₂PtCl₆ at a lower concentration, while with the increment of the amount of H₂PtCl₆, the sizes may increase and the shapes of the NPs may change to cuboid (5-6 nm), oval (6-8 nm), and flower (16-18 nm) ⁸.

PtNPs may be prepared following the methodology ⁵⁶:Firstly, K₂PtCl₄ solution (20 mM, 5 mL) is mixed with Brij 58 solution (0.044 M, 1 mL), followed by sonication for 10 min utilizing a bath sonicator. Afterthat, L-ascorbic acid solution (0.04 M, 5 mL) is poured into the previous solution followed by sonication for 45 min. Then the precipitates are collected through centrifugations for 3 times. Following another methodology ⁵⁷, PtNPs may be synthesized by the chemical reduction of the platinum salt (H₂PtCl₆.6H₂O (2 mmol L^-1)) with the reaction of sodium borohydride (NaBH₄ (4 mmol L^-1)) utilizing poly vinyl alcohol as the capping stabilizer agent. The mixture is kept under vigorous stirring for 18 h for complete reduction, while the color of the mixture becomes bright yellow indicating the colloidal formation of NPs with the characteristic UV-Vis spectrum absorption peak at 260 nm. Following other method ⁵⁸, PtNPs may also be synthesized through the reduction of H₂PtCl₆ (5 mM, 19.5 mg) with C₆Na₂O₆ (43.5 mM, 83 mg) for 1 h at 90◦C. 

Hybrid Au-Pt NPs may be synthesized through the reduction of Na₂PtCl₆.6H₂O by ascorbic acid ⁵⁹. At first, AuNPs solution is heated at 90◦C for 10 min, and Na₂PtCl₆.6H₂O (1mM, 0.32 mg) and ascorbic acid (4 mM, 28 mg) are adjoined step by step at 10 and 30 min periods. Afterthat, the reaction mixture is heated at 90◦C for 30 min. The Au-Pt NPs are also synthesized following two synthetic methods: 1. In this synthetic approach, two steps of the formation of Au-Pt NPs are considered. Firstly, the AuNPs are synthesized and purified ^60-64. Secondly, PtNPs are formed: 18mL Milli-Q H₂O and 5 mL purified AuNPs are placed in a 50 mL round bottom flask and stirred at 100◦C for 15 min until stabilization. Then 1 mL trisodium citrate dihydrate (68 mM, 0.020 g) is added to the solution and allowed for 10 min for temperature homogenization. Afterthat, 1 mL potassium tetrachloroplatinate (II) (K₂PtCl₄) (4.2 mM, 0.0017 g) is added, while a change of color to bluish-purple is observed, and after 3 h of the reaction, the colloidal dispersion shows a final purple color. The colloidal mixture is spun at 15,000 rpm (10 min, 1 cycle), and the precipitate is isolated from the supernatant. The supernatant denotes the colloidal solution with the coveted NPs. 2. In this method, a one-step formulation of Au-Pt NPs is followed, while platinum-precursor is adjoined to the flask after AuNPs are formed: 22.75 mL Milli-Q H₂O is poured in a 50 mL round bottom flask affixed to a condenser and 100◦C. 250 µL aqueous solution of HAuCl₄xH₂O (25.4 mM, 0.00216 g) is added into the flask after stabilization of the temperature.Then 1 mL aqueous solution of trisodium citrate dihydrate (68 mM, 0.020 g) is added and allowed for homogenization of temperature. Afterthat, 1 mL potassium tetrachloroplatinate (II) (4.2 mM, 0.017 g) is added into the flask for reaction. The suspension is spun at 15000 rpm (10 min, 1 cycle), and the precipitate is isolated from the supernatant. The supernatant denotes the colloidal solution with the wanted NPs. 

  The Fe-Pt NPs may be synthesized following different methodology ⁴⁶: FePt NPs may be prepared following polyol reduction method, while a reaction mixture of Fe(CO)₅, Pt(acac)₂, dioctyl ether, 1,2-hexadecanediol, oleic acid and oleylamine is heated at 290◦C and then utilizing ethanol to extract resultant FePt NPs. An equimolar ratio of a Fe precursor (Fe(acac)₃) and Pt precursors (Pt(acac)₂, PtCl₂, PtCl₄, and H₂PtCl₆.H₂O) and the reducing agent (1,2-hexadecanediol) with octyl ether may be utilized to get diverse sizes of Fe-Pt NPs. Fe-Pt NPs may also be prepared using microemulsion method in a water/glycol octyl phenyl ether/cyclohexane (water-in-oil) microemulsion utilizing FeCl₂ as the Fe precursor, H₂PtCl₆ as the Pt precursor and NaBH₄ as the reducing agent.

  Bio/green synthesis of PtNPs mediated by plant-extracts involving plant derivatives and metal precursors at optimal pH and temperature requires four hypothesized essential steps ⁶⁵: The initial activated bio-reduction of metal ions to zero-oxidation states by plants-reducing agents; The 2^nd stage includes the development and aggregation of produced tiny particles into NPs having higher thermal stability; The 3^rd termination step involves stabilized and capped NPs by plant derivatives having controlled range of shapes and sizes; The 4^th stage includes cleansing and purification of the NPs through centrifugation. The optimization of the shape, size, morphology and crystallinity of the NPs may be controlled by regulating reaction time, pH and temperature.

  The green synthesis of PtNPs using plant-extracts (derivatives such as flavonoids, antioxidants, phenolic compounds, gallic acids, ascorbic acids, terpenoids, amino acids and a few proteins used to function as reducing, stabilizing or capping agents) and platinum precursors such as H₂PtCl₆ is performed through the reaction at 50-100◦C for 1-5 h to get different optimized morphological NPs. The changes of color from yellow to brown confirms the formation and completed reduction of Pt⁴ ions to Pt⁰ NPs analyzed by UV-Vis spectroscopy at 477 nm ^66-72.

Surface functionalizations of platinum nanoparticles and their hybrid forms 

Surface functionalizations (Fig.1) such as ligand exchange/addition, bio or chemical conjugations are needed for improved biocompatibility, excellent dispersion, prolonged circulation, specific targeting and sustained cargo release. Moreover, inclusion of reactive functional groups to the surfaces of NPs for further conjugation may make NPs multifunctional. The materials used for surface modification of metallic NPs to enhance their specificity and efficacy with therapeutic and catalytic activity include organic micromolar compounds such as aspartic acid, citric acid, glutamic acid, phosphorus acid, 2-amino ethyl mercaptan, gamma cyclodextrin and vitamin B, organic polymer compounds such as starch, glucose, polyethyleneimine (PEI), polyethylene glycol (PEG), polypeptides, proteins, and polyvinyl alcohol (PVA), low-molecular-weight ligands, polyunsaturated and saturated fatty acids, siRNA, DNA, plasmids, antibodies, small molecules, tumor markers and SiO₂, and inorganic nanomaterials such as Au and Fe ^73-79.

 

 

Figure 1: Functionalized PtNPs via conjugation of peptides, nucleic acids, antibodies, folic acid, biomolecules, polymers, and tumor markers.

 

 

A few functionalizations of PtNPs are described below: 

The encapsulation of PtNPs with PLGA may be performed with some modifications by double emulsion ⁸⁰. Different amounts of PtNPs and PVA (0.5% w/v) are adjoined to 200 µL ultrapure water for forming the 1^st aqueous phase. 10 mg PLGA is dissolved in 0.4 mL dichloromethane to prepare an organic phase. Afterthat, the aqueous phase is added drop by drop into the organic phase and emulsified for 1 min with sonication at 25 W and 30% amplitude utilizing a sonicator. Then the first emulsion is added drop by drop into the PVA solution (1.6 mL, 1% w/v). The final solution is emulsified again through the sonication at 25 W and 30% amplitude for 2 min (second emulsion). Lastly, the second emulsion is stirred overnight at room temperature for removing the solvent. The NPs are collected through centrifugation and cleansing with ultrapure water three times. 

  The surface modifications of PLGA encapsulated PtNPs are performed through the attachments of the antibody and the PEG, such as, cetuximab to the PLGA particles: The previously prepared freeze-dried particles are redispersed in 1 mL MES buffer solution (containing 0.4 mg EDC) and waited to react with EDC for 10 min at room temperature on a rotator. Afterthat, 20µL solution of 1.1 mg sulfo-NHS with 40 µL MES is added to the particle solution, vortexed and allowed to react for 10-15 min at room temperature on the rotator. Then the particles are spun at 22136 RCF for 1 h, and the supernatant is removed, and 1 mL PBS is adjoined for sonication. Different amounts of 5 kDa PEG and 3 kDa PEG-biotin are adjoined into the solution and allowed to react for 2 h at room temperature on the rotator. Lastly, for the removal of the excess amount of PEG, unreacted particles are cleansed 3 times through centrifugation at 22136 RCF for 1 h with the replacement of the supernatant with PBS. The biotin-labeled antibody is anchored to the particles via conjugation with neutravidin: A solution of neutravidin (10 mg) in 0.5 mL 0.1% Tween-PBS is added into a well on a 4-well plate with a stir-bar. The particles sonicated previously are adjoined drop by drop into the neutravidin solution and waited to react for 3 h at room temperature. Then the solution is spun at 22136 RCF for 1 h and cleansed 3 times with PBS for the removal of the unreacted neutravidin. Afterthat, the particles are sonicated and 13.3 µL of biotin-antibody is adjoined into the tube and allowed to react for 3 h at room temperature on a rotator. Finally, the particles are spun at 22136 RCF for 1 h and cleansed 3 times in PBS for the removal of the unreacted antibody.

  Au-Pt NPs may be coated with 3-aminopropyl trimethoxy silane (APTMS) and loaded with drug such as quinazoline derivative (Qd) following the method ⁸¹: 1mL Au-Pt NPs colloidal solution, 8 mL methanol and 2 mL Milli-Q water are mixed in a 25 mL round bottom flask. 0.6 mL APTMS is adjoined into the reaction solution and allowed to stir for 30 min at room temperature (RT) followed by stirring at 4◦C of the colloidal yield. Afterthat, 5 mL dimethyl sulfoxide (DMSO) is poured into a vial containing 2-(quinazolin-4-ylamino) propanoic acid (Qd) (0.026 mmol, 5.56 mg) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (0.020 µmol, 0.020 mL) and sonicated until fully dissolved. On the other hand, 7.5 mL Au-Pt-APTMS NPs is poured in a 50 mL round bottom flask containing 7.5 mL Milli-Q water (ratio 1:1) and dispersed under magnetic stirring at RT. After 5 min, the solution of DMSO with the Qd and the EDC is adjoined into the flask followed by the addition of 2-3 drops of 0.1 M NH₃ until the pH reaches to 11, and allowed the reaction under magnetic stirring overnight at RT to acquire the Qd-functionalized NPs. The NPs obtained are purified through dialysis ^63-65. The purified hybrid Au-Pt NPs solution may be incubated with drug such as doxorubicin at pH 8 as drug loading by its deprotonation at basic pH ⁸². The PEG may be coated on the NPs to remove particle aggregation and enhance the colloidal stability ⁸³. Additionally, the bifunctionalized PEG linkers can enable the nanovehicles’ active targeting characteristics conjugated to cRGD peptides. 

  The surface functionalizations of Fe-Pt NPs through the ligand exchange of fromoleic acid to aminoethanethiol (AET), and the conjugations of anti-Her2 antibody and / or cysteamine, silica and (3-aminopropyl) triethoxy silane, tetraglycol, 3-mercaptopropionic acid (MPA) to produce COOH-terminated with EDC and folic acid, poly (diallyldimethylammonium chloride (PDDA) and silica, poly(L)lysine (PLL), folate, PEG, HVGGSSV peptide and Alexa fluor 750 fluorescent probe, oleic acid/oleylamine and L-cysteine, or synthesized FePt-Fe₂O₃ with PEG and folate, have been performed to get excellent water-solubility with no aggregation in dispersion, excellent biocompatibility and stability, higher photothermal transduction efficiency, higher specific targeting therapeutic anticancer efficiency, and radiation-guided targeting/imaging and drug release into the diseased site/s ^{84-90,47,51,52}. 

Characterization of the platinum nanoparticles and their composites

  The synthesized Pt NPs/composites may be characterized by various analytical techniques ^55,91,92. UV-Visible spectroscopy is utilized for confirming the synthesis and stability of the metallic/colloidal NPs. High resolution transmission electron microscopy is used to detect the morphology, crystal core-shell structure, size, and the quantitative and qualitative analysis of the prepared and internalized NPs in cells or tissues. Atomic force microscopy is utilized to determine the surface thickness of the nanomaterials. Scanning electron microscopy is used to measure the structure of the surface and dimension of the NPs. Electrophoretic light scattering technique is utilized for the measurement of the electrophoretic mobility of NPs in dispersion, or in solution. X-ray diffractometry is used to evaluate the crystalline nature of the functionalized NPs. Energy-dispersive spectroscopy is utilized to analyze the elemental composition of metallic NPs. Extended X-ray absorption fine structure spectroscopy is utilized for the elemental analysis of inter atomic distance and structural disorders of the NPs. Nanoscale infrared spectroscopy is used to detect the elemental composition and the bonding arrangement of the NPs. Fourier transform infrared spectroscopy is used to measure the concentration of the chemicals, surface chemistry, functional groups and atomic arrangement of the NPs. Dynamic light scattering spectroscopy is utilized to determine the hydrodynamic diameter/size and the surface charge/zeta potential for confirming contrast PEG attachment of the NPs. The inductively coupled plasma-atomic emission spectroscopy is used to measure the proportion of Au and Pt contents of the hybrid NPs. For visual characterization regarding the attachment of the secondary antibody, nanoparticle tracking analysis is utilized with a 488 nm laser, in fluorescent mode with a 500 nm filter for antibody-conjugated NPs. Computed tomography imaging is utilized to examine the concentration-dependent contrast signaling of the hybrid NPs.

Mechanism of action of platinum nanoparticles

The microbicidal action of PtNPs may occur through their attachments to microbial surfaces and penetration to cell wall causing their disruption and lysis. These activities are associated with the intercellular ROS production (^.OH, O₂^.-) leading to enzyme denaturation, DNA and cellular damage ^93,94. The anti-cancer activity of PtNPs may occur through their passive or active targeting inside the cells causing DNA strand breaks via the generation of ROS leading to DNA damage, intracellular macromolecules (such as carbohydrates and proteins) damages, disruption of DNA repair mechanisms and inhibition of gene transcription leading to growth arrest and apoptosis ^95-98. Free radicals such as H₂O₂ and O₂^.- generated into the cellular cytosol and mitochondria are regulated by the intrinsic enzymes such as catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) to arrest oxidative stress, while SOD dismutes O₂^.- into H₂O₂ and O₂, POD decomposes H₂O₂ into H₂O, and CAT reduces H₂O₂ into O₂ and H₂O. The PtNPs possess SOD, POD and CAT-like enzymatic antioxidant activities to scavenge ROS and reduce cellular oxidative damage without any release of ^.OH via the Fenton reaction ⁹⁹.

Biomedical applications of platinum nanoparticles and their composites

  A few reports of different groups on therapeutic efficacy regarding, chiefly, on cellular killing of Pt/hybrid Pt NPs against different diseases/cancers based on active or passive targeting have been described below (Table 1):

  A few researchers have utilized different Pt/hybrid NPs such as PtNPs, AgPt NPs, PtNPs, PtNPs-based microreactors, AuPt NPs, H₂PtCl₆/SiO₂ and H₂PtCl₆/TiO₂ with their various sizes to treat cancer cells or target in vivo animals such as A549, MDA-MB-231, LNCaP; HDF, A375, U87; Neuro 2A; SH-SY5Y; S1, S2, SP56 and C6, tumor bearing male Wistar rats respectively for getting higher therapeutic and targeting efficacy against brain cancer ^100-105. A few investigatorshave used several NPs such as PtNPs, FA-Pt NPs, AuPt NPs, FA-FePt NPs, Fe₃O₄-Pt NPs, PIMA-CIS NPs, PEG-PIMA-CIS NPs, Pt@Bi₂Te₃-PEG NPs, and PSDE-Co-LDI-Pt(IV) NPs with their different sizes against HeLa, MDA-MB-231, 4T1, MCF-7, SKOV3(HER2+), MDA-MB-231(HER2-), EMT-6, SKBR3, WM-266-4, LLC and A549 (CIS sensitive) cells, and to treat in vivo tumor bearing animals for getting higher anticancer targeted efficacy to combat breast cancer ^9,51,106-115. A few scientists have applied different NPs such as PEGuilada-Pt NPs, TPP-Pt NPs, FA-Pt NPs, FePt NPs and peptide-gHPt2.5 NPs with their various sizes to treat HeLa, SiHa, and vero cells for getting targeted higher anti-cancer and antioxidant efficacy against cervical cancer ^{53,103,109,116-118}. A few other investigators have utilized PtNPs with different sizes against K562, HepG2 and HuH-7 cells and to treat invivo tumor xenograft animals for getting higher anti-cancer efficacy in liver cancer ^40,119,120. A few other researchers have applied PtNPs against Mia-Pa-Ca-2 cells to achieve higher therapeutic efficacy against pancreatic cancer ¹²¹. A lot of researchers from different groups have applied various Pt/hybrid Pt NPs such as PEI-PCL-PEG micelleplexes, porous Pt NPs, PtNPs, HA-BPEI-SS-Pt NPs, FePt-Cys NPs, liposomal cisplatin (CIS) NPs and PLGA-carboplatin NPs with their different sizes to treat lung cancer cells, NSCLC, A549, human non-small lung cancer cells, H1975, LLC, NCI-H596, MA148, NCI-ADR/RES, MDA-MB-231 cells, and in vivo tumor models for achieving higher anti-cancer efficacy against lung cancer ^122-130. A lot of other researchers from different groups have used several NPs such as PtNPs, AuPt NPs, AuPtNCs and MgO-Pt NPs with their different sizes for treating various cells such as A549, HT29, human colon carcinoma cells, HCT-116, SW480 and SW62 cells to get higher targeted therapeutic efficacy against colon cancer ^131-136. A lot of investigators have utilized different Pt/hybrid Pt NPs such as PtNPs, PLGA-carboplatin NPs, PLGA-PEG-wortmannin-CIS NPs, CIS NPs, FePt NPs, and metal-organic cages NPs with their different sizes for the treatment of various cancer cells such as SKOV-3, PA-1, OC SKOV-3, PROC, A2780, human ovarian cancer cells and in vivo tumor models to get higher targeted therapeutic efficacy against ovarian cancer ^121,137-143. A few investigations have been performed through utilization of AuPt nanoseeds and AuPdPt NPs with their different sizes to treat EJ and bladder cancer cells for achieving higher anti-cancer efficacy against bladder cancer ^144,145. Another investigation has been done by using melanin-loaded Pt(IV) NPs to treat PC3 cells and in vivo tumor model for getting higher therapeutic efficiency against prostate cancer ¹⁴⁶. A few researchers have utilized liposomal cisplatin to treat squamous cell oral carcinoma and in vivo tumor bearing animals for achieving higher targeted therapeutic efficacy against oral squamous cell cancer ¹⁴⁷. A few other researchers have used PtNPs to treat U20S cells to get higher targeted anticancer efficacy against bone cancer ¹⁴⁸. A few investigators have used PtNPs and PCL-Pt NPs to treat U937 and HH carcinoma cells for getting higher therapeutic efficacy against lymphoma ^149,150. Another group of researchers have utilized PtNPs to treat B16/F10 cancer cells for getting higher therapeutic efficiency against melanoma ¹⁵¹. A few researchers have used PtNPs to treat human acute monocytic leukemia cells to achieve higher anticancer efficiency against leukemia ¹⁵². A few investigations have been performed utilizing PVP-Pt NPs to treat Gram +ve/-ve bacterial strains for getting higher microbicidal efficacy against microbial disease ^153,154. Another group of researchers have utilized PtNPs to treat in vivo animals for getting higher therapeutic efficacy against colitis ¹⁵⁵.

 

 

Table 1: A few therapeutic effects of platinum and hybrid platinum nanoparticles against various cancers/diseases/microbial strains.

Cancers/Diseases/ Microbial strains	Platinum/Hybrid Platinum NPs	Particle sizes (nm)	Cell lines/Animal models/ Microbial strains	Ref
Brain	PtNPs AgPtNPs PtNPs PtNPs-based microreactors AuPtNPs H2PtCl6/SiO2 H2PtCl6/TiO2	20-110 42±11 1-21 2 50 1.7 3.1	A549, MDA-MB-231, LNCaP HDF, A375, U87 Neuro 2A SH-SY5Y S1, S2, SP56 C6, Male Wistar rats	100 101 102 103 104 105
Breast	PtNPs PtNPs PtNPs PtNPs FA-PtNPs AuPtNPs FA-FePtNPs Fe3O4-PtNPs PIMA-CISNPs PEG-PIMA-CISNPs Pt@Bi2Te3-PEG PSDE-co-LDI-Pt(IV)NPs	1-6 15 45 20,12 10-15 30 12±1.0 4 80-140 80-140 80 156	HeLa, MDA-MB-231 4T1 MCF-7 MCF-7 MCF-7 SKOV3(HER2+), MDA-MB-231(HER2-) EMT-6 SKBR3, WM-266-4 LLC, 4T1 4T1, In vivo 4T1 A549 (CIS sensitive), In vivo toxicity	106 107  108 9 109 110 51 111 112 113 114 115
Cervical	PEGuilada-PtNPs TPP-PtNPs FA-PtNPs FePtNPs Peptide- gHPt2.5NPs	34.8±5.3 30-60 10-15 3.11±0.53 2.5	HeLa SiHa HeLa Vero, HeLa Antioxidant activity in HeLa cells	103 116  117 109 53 118
Liver	PtNPs PtNPs PtNPs	86 20-40 6.30±2.4	K562,HepG2,Tumor xenograft murine model HepG2, In vivo HuH-7	40 119 120
Pancreas	PtNPs		Mia-Pa-Ca-2	121

 

 

 

 

Table 1. Continued 1.

Cancers/Diseases/ Microbial strains	Platinum/Hybrid Platinum NPs	Particle sizes (nm)	Cell lines/Animal models/ Microbial strains	Ref
Lung	PEI-PCL-PEG micelleplexes Porous PtNPs PtNPs PtNPs HA-BPEI-SS-PtNPs   FePt-Cys NPs PtNPs Liposomal CIS NPs PLGA-carboplatinNPs	160 115.6 20 4-12 160-230   26.4     120-140   300	Lung cancer cell line NSCLC, In vivo A549 A549 Human non-small lung cancer cells, In vivo tumor model A549, H1975, LLC, In vivo A549, In vivo NCI-H596, NSCLC MA148, A549, NCI-ADR/RES, MDA-MB-231	122 123 124 125 126   127 128 129 130
Colon	PtNPs PtNPs PtNPs AuPtNPs AuPtNCs MgO-Pt NPs	40 100   99.54 20 30-50, 932.3±22	A549 HT29 Human colon carcinoma cells HCT-116 SW480, SW62 A549, HT29	131 132 133 134 135 136
Ovarian	PtNPs PtNPs PLGA-carboplatin NPs PLGA-PEG-wortmannin-CIS NPs CIS NPs FePtNPs Metal-organic cages NPs	30-70   222±1.1 80-200 70±30 80 98±8.2	SK-OV-3 PA-1 OC SKOV-3 Pt-resistant ovarian cancer (PROC), In vivo SKOV3, In vivo A2780 Human ovarian cancer cells	137 121 138 139 140 141,142 143
Bladder	AuPtnanoseeds AuPdPtNPs	10-50 30	EJ Bladder cancer	144 145
Prostate	Pt(IV)-Melanin NPs	73.7	PC3, In vivo	146
Oral squamous	CIS-liposome	35±0.8	Squamous cell oral carcinoma, In vivo	147
Bone	PtNPs	30	U20S	148
Lymphoma	PtNPs PCL-PtNPs		U937 U937, HH	149 150
Melanoma	PtNPs	12.2±0.7	B16/F10	151
Leukemia	PtNPs	30	Human acute monocytic leukemia cells	152
Microbial	PVP-PtNPs	10-60	Gram+/- bacterial strains	153,154
Colitis	PtNPs	5,30,70	In vivo	155

 

 

  A lot of reports on anti-cancer therapeutic efficacy (mainly cellular killing and / or growth inhibition) of PtNPs used for the delivery of different anti-cancer agents to treat various cell lines/animal models against different cancers/tumors have been depicted below (Table 2):

  A few researchers have utilized different anti-cancer agents such as AuPt NPs/AuPtQ NPs, FePt-OA/OA-Cys NPs, and FePt-Cys NPs with their different particle sizes to treat U87-MG, D54, U251, U87, H4, SGH44, and C6 cells to get higher anti-cancer efficacy against brain cancer ^156,52,49. A few scientists have used Pt-Au NRs, and Apt-Alb-CIS NPs with their different sizes to treat SW620, SW480 and HeLa cells, and in vivo cervical cancer model for achieving higher therapeutic efficacy against cervical cancer ^157,158. A few investigators of different groups have applied DOX-Fu-Pt NPs, GO-Pt NPs, PIMA-GA-DACH-Pt NPs, AuPt-cRGD/DOX-AuPt-PEG/DOX-AuPt-cRGD/NIR Laser, PEG-Pt-DOX NPs and PVP-Pt-DOX NPs, chitosan/zinc/silica/DOX/telmisartan-Pt NPs, and four Pt(II)iron oxide NPs with their different sizes for treating MCF-7/ADR, LNCaP, MCF-7, HepG2, HeLaB, HT29, HCT116,SW480, Colo 205, CP20, 4T1, MDA-MB-231 and IGROV-1 cells, and in vivo, in vivo 4T1-tumor model and MDA-MB-231-xenograft models to get higher anti-cancer therapeutic efficiency against breast cancers/tumors ^{159-165, 91,36,55}.

 

 

Table 2. Platinum nanoparticles utilized for delivery of anti-cancer agents to various cancers/tumors.

Cancers	Anti-cancer agents	Particle sizes (nm)	Cell lines/Animal models	Ref
Brain	AuPt NPs/AuPtQ NPs FePt NPs coated with oleic acid/oleylamine (OA/OA) and cysteine (Cys) L-Cys coated FePt (FePt-Cys) NPs	50/100 µm 3-8    245  / 4.8±0.6	U87-MG, D54, U251 U87, U251, H4   SGH44, C6, U251	156 52   49
Cervical	PtAunanoraspberries (NRs) Apt-Alb-CIS NPs (EGFR-targeted albumin-cisplatin NPs with EGFR aptamer)	10    80	SW620, SW480   HeLa, In vivo cervical cancer model	157   158
Breast	DOX-loaded FuPtNPs (Fucoidan-coated PtNPs) GOPtNPs (Graphene oxide functionalized with PtNPs)   PIMA-GA-DACH-PtNPs AuPt-cRGD/DOX-AuPt-PEG/DOX-AuPt-cRGD/NIR Laser PEG-Pt-DOX NPs PVP-Pt-DOX NPs Chitosan/zinc/silica /DOX/telmisartan-Pt NPs   Four Pt(II)iron oxideNPs: PEG-GLU-Pt-DACH, PEG-Glu-Pt-EDA, PEG-Mal-Pt-DACH, PEG-Mal-PT-EDA	33±3.4    2-19    80-250      120±5        27-100	MCF-7/ADR,  In vivo   LNCaP, MCF-7, HepG2, HeLaB, HT29, HCT116, SW480, Colo205 CP20, 4T1, MDA-MB-231, In vivo 4T1 breast cancer tumor model   MDA-MB-231 tumor cells/xenograft models   ADR/MCF-7 MCF-7, MDA-MB-231 In vivo breast cancer model   IGROV-1,MDA-MB-231	159   160   161   91   36   55,162   163,164   165
Liver	DNR-Pt NPs Peptide-Pt NPs GA-ALG-Pt NPs	11.38±2.67  2.5 141.9	HepG2/xenograft model HepG2 HepG2	40 166 167

 

 

A few other groups of researchers have used DNR-Pt NPs, peptide-Pt NPs, and GA-ALG-Pt NPs with their different sizes to treat HepG2 cells and xenograft model for getting higher anti-cancer efficacy against liver cancer/tumor ^40,166,167. A few other investigators have applied different anti-cancer agents such as TPGS-Pt NPs, HA-GEM/CH-Pt NPs, chitosan-Pt NPs, CDDP-NPs, PEG-Pt-CNPs, GP-NA, OAPI, USPtNs, and PDDA-silica-DOX-FePt NPs with their different sizes to treat Pt-resistant DDP/A549, NCI-H460, A5491, A549, HeLa, LLC, A549/U14, NCI-H1299 and RERF-A1 cells, and in vivo tumor cells-bearing animals to achieve higher anti-cancer efficiency against lung cancer ^168-173,50. A few other scientists have utilized polyphenol-Pt NPs, LP-Pt NPs, CIS-Pt-BR NPs, and DACH-Pt(II)-panitumumab NPs with their different sizes to treat HCT-116, HT-29, Caco2 cells, and in vivo tumor cells-bearing animal models for achieving higher anti-cancer efficacy against colon cancer/tumor ^174-177. An investigation has utilized PPNPs-siRNA to treat A2780 cells to get higher anti-cancer efficacy against ovarian cancer ¹⁷⁸. Another investigation has used Apt-polymer-Pt NPs and PLGA-b-PEG-Apt-Pt NPs for the treatment of LNCaP and PC3 cells, and in vivo tumor cells-bearing animals to get higher anti-cancer efficacy against prostate cancer ^179,180. One group of researchers have used PA-Pt NPs to treat PC-9 and NIH-3T3 cells, and in vivo animal model for achieving higher anti-cancer efficacy against bone cancer ¹⁸¹. 

 

 

 

Table 2. Contd.1

Cancers	Anti-cancer agents	Particle sizes (nm)	Cell lines/Animal models	Ref
Lung	TPGS-Pt NPs HA-GEM/CH-Pt NPs Chitosan-Pt NPs CDDP-NPs PEG-Pt-CNPs GP-NA, OAPI, USPt Ns PDDA-silica-DOX-FePt NPs	85.3 200 230-270 36.7±8.1 18.7±4.6 165.4±2.6	Pt-resistant DDP/A549 NCI-H460, In vivo A5491, A549 HeLa, LLC, In vivo A549 / U14, In vivo A549, NCI-H1299, In vivo RERF-A1	168 169 170  171 172  173 50
Colon	Polyphenol-Pt NPs Lycopene(LP)-Pt NPs CIS-Pt-BR NPs DACH-Pt(II)-panitumumab NPs	10-70 <50 192±88 120-155	HCT-116 HCT-116 HT-29,  In vivo HCT116, HT29,Caco2, In vivo	174 175 176  177
Ovarian	PPNPs-siRNA	110	A2780	178
Prostate	Apt polymer-Pt NPs PLGA-b-PEG-Apt-PtNPs	140 150±15	LNCaP, PC3 LNCaP, In vivo	179 180
Bone	Phytic acid(PA)-Pt NPs	1.7±1.2	PC-9, NIH-3T3, In vivo	181
Oral squamous	PtNCP (Pt- nanocomposite beads)		Oral squamous carcinoma cells, Animal tumor xenograft model	182
Melanoma	PEG/DOX-Pt NPs	40-45	A549, B16F10, NIH-3T3, In vivo tumor model	183
Choriocarcinoma	Folate-Pt(IV)-SWNT (Single wall carbon nanotube)		JAR cells	184
Gastric	PDDA/silica/DOX-FePt NPs		MKN-74	50
Leukemia	CIS/DNR-Pt NPs	11.38±2.6	K562, K562 tumor-bearing mice	40

 

 

Another group of researchers have utilized PtNCP to treat squamous carcinoma cells and animal tumor xenograft model for getting higher anti-cancer efficacy against oral squamous cancer¹⁸². PEG/DOX-Pt NPs have been utilized by some researchers to treat A549, B16F10 and NIH-3T3 cells, and in vivo tumor model to achieve higher anti-cancer therapeutic efficacy against melanoma ¹⁸³. Folate-Pt(IV)-SWNTs have been used by some other researchers to treat JAR cells for getting higher anti-cancer efficiency against chorio carcinoma ¹⁸⁴. PDDA/silica/DOX-FePt NPs have been applied by some investigators to treat MKN-74 cells for getting hugher anti-cancer efficacy against gastric cancer ⁵⁰. CIS/DNR-Pt NPs have been utilized by some other investigators to treat K562 cells, and K562 tumor bearing mice for achieving higher anti-cancer efficiency against leukemia ⁴⁰. 

Toxicity of platinum nanoparticles

The cytotoxicity of the PtNPs is generally dependent on their sizes, shapes and concentrations used ⁵⁶ [60]. Several investigations have explored that PtNPs having 50 nm size show anti-cancer effect, while their sizes belonging to 5 and 20 nm exhibit no anticancer effect ¹⁸⁵. The viability of cancer cells (MDA-MB-231 (TNBC)) by the exposure of PtNPs (10 µg/mL) has been observed to 80%, whereas that value has been decreased to 2% by the exposure of PtNPs at 200 µg/mL after five days of incubation, while their cytotoxicity with healthy cells (NHCF-V (fibroblasts)) has exhibited no statistically significant differences after five days of incubation at all concentrations, indicating their sensitive specificity to cancerous cells¹⁸⁵. Mice treated with PtNPs at higher concentration have shown their proinflammatory responses through the enhancement of various cytokines such as TNF-α, IL-1, IL-2, IL-4-6, and IL-12, with concomitant reduction of intracellular GSH ¹⁸⁶. Mice treated with PtNPs (maximum 10 µg/mL concentration) have exhibited no significant changes in the activation of T cells, T helper cells (CD3+/CD4+) and cytotoxic T cells (CD3+/CD8+) in the 1^st 72 h and after long-term treatment, and also no activity of natural immune killer cells (NK, CD49b+/Granzyme B+) after twelve weeks, implicating their favorable biocompatibility⁴⁰. AuPt NPs (10,30,50 and 100 µM) treated with different cell lines such as HEK-293 (human embryonic kidney cells as control), U-87-MG and D54 (both wild type human glioblastoma cells), and U251 (PTEN-mutant human glioblastoma cells) for 24 h have exhibited decreased viability indicating their in vitro cytotoxicity ¹⁵⁶. FePt NPs (3,6 and 12 nm) with a concentration of 100mM have shown their higher cytotoxicity (75% cell viability), while no remarkable cytotoxicity (cell viability >90%) at their concentrations below 10 mM ⁴⁷.

Biodistribution and elimination

Generally, the biodistribution profiles depend on the NPs’ size, coating and attachment with other ligands, concentration, exposure time, and route of administration, and systemic pathophysiological conditions. One investigation regarding biodistribution analysis in six-week-old male C3H/HeN mice has exhibited that the most of the FePt NPs (3,6 and 12 nm) have been accumulated chiefly within the spleen followed by lung and liver, and their gradual excretion from the organs with time (about one week), while 12 nm FePt NPs have shown their highest serum concentration and circulation half-life, and 3 nm FePt NPs have shown their highest brain concentration ⁴⁷. Another study (short term biodistribution) using BALB/c mice exposed with single intravenous tail-vein injection of Pt NPs (10 mg/kg body weight) for 24 h has shown the accumulation of NPs in the liver, spleen, kidney and lungs, but not in plasma ¹⁸⁷. The long term biodistribution study has exhibited that the Pt NPs (10 mg/kg body weight) administered intravenously have shown their highest accumulation after 21 days in the liver and spleen, and residual in the other organs such as kidney, lungs and heart ¹⁸⁷. Generally, endocytosed NPs are processed to brokens within the phagolysosomal compartment and excreted via hepato-pancreatic biliary system and the small intestine as fecal clearance, while non-decomposed larger NPs (>6 nm) are sequestered mainly in the spleen and liver for several months or excreted via the glomeruli (<5 nm) ¹⁸⁸.

Conclusions and future perspectives

In general, PtNPs show their specific cytotoxic effect in in vitro diseased cell lines compared to healthy cells.  As PtNPs show their cytotoxicity at higher concentration and for long term exposure in in vivo, their surface-functionalizations with polymers or other ligands for applications are more suitable for getting higher antimicrobial/anticancer efficiency and to get targeted therapy for reducing systemic toxicity and sustained drug release accompanying antioxidant activity against diseases. In this concern, NPs should be optimized with more controllable and uniform sizes for having enhanced biocompatible stability regarding their synthesis, functionalization, and characterization, and repeated batch-to-batch uniformity of the development of NPs before application to get higher suitable therapeutic efficacy. A thorough investigation regarding the NPs’ source of raw materials, method of productions, consistent scale-up process, solubility, biocompatibility, stability, route of in vivo administration, biodistribution, pharmacokinetics, elimination, accumulation, cell-specific targeting, controlled release and toxological issues to human beings with high consistency is required before clinical translation to consider PtNPs as drug delivery system as well as nanomedicine for achieving maximum biological effectiveness against diseases. 

Conflict of interest 

The author declares no conflicts of interest. 

Acknowledgement

This study was supported by the Council of Scientific and Industrial Research (CSIR), Government of India.

References

1. Mandal AK. Dendrimers in targeted drug delivery applications: A review of diseases and cancer. Int J Polym Mater Polym Biomater. 2021; 70(4):287-97. https://doi.org/10.1080/00914037.2020.1713780

2. National Institutes of Health (US). Biological sciences curriculum study NIH curriculum supplement series. In understanding emerging and re-emerging infectious diseases: National Institutes of Health (US). 2007; Bethesda, MD. https://www.ncbi.nhm.nih.gov/books/NBK 20370/ (accessed on 20 April 2017).

3. Waarts MR, Stonestrom AJ, Park YC, Levine RL. Targeting mutations in cancer. J Clin Invest. 2022; 132(8):e154943. https://doi.org/10.1172/JCI154943 PMid:35426374 PMCid:PMC9012285

4. Jin J, Wu X, Yin J, Li M, Shen J, Li J, et al. Identification of genetic mutations in cancer: Challenge and opportunity min the new era of targeted therapy. Front Oncol. 2019; 9:263. https://doi.org/10.3389/fonc.2019.00263 PMid:31058077 PMCid:PMC6477148

5. Rivas-Dominguez A, Pastor N, Martinez-Lopez L, Colon-Perez J, Bermudez B, Orta ML. The role of DNA damage response in dysbiosis-induced colorectal cancer. Cells. 2021; 10(8):1934. https://doi.org/10.3390/cells10081934 PMid:34440703 PMCid:PMC8391204

6. Gao Y, Shang Q, Li W, Guo W, Stojadinovic A, Mannion C, et al. Antibiotics for cancer treatment: A double-edged sword. J Cancer. 2020; 11(17): 5135-49. https://doi.org/10.7150/jca.47470 PMid:32742461 PMCid:PMC7378927

7. Mandal AK. Gold nanoparticles as theranostic delivery system in combating various diseases. In Book: Tsygankova Victoria Anatolyivna, Editor. "Research Advances in Microbiology and Biotechnology Vol. 6". India-United Kingdom:Book Publisher International.2023;cp 8, pp 100-128. https://doi.org/10.9734/bpi/ramb/v6/5933B

8. Gopal J, Hasan N, Manikandan M, Wu HF. Bacterial toxicity / compatibility of platinum nanospheres, nanocuboids and nanoflowers. Sci Rep. 2013; 3:1260. https://doi.org/10.1038/srep01260 PMid:23405274 PMCid:PMC3569627

9. Sahin B, Aygun A, Gunduz H, Sahin K, Demir E, Akocak S, et al. Cytotoxic effects of platinum nanoparticles obtained from pomegranate extract by the green synthesis method on the MCF-7 cell line. Coll Surf B Biointerfaces. 2018; 163:119-24. https://doi.org/10.1016/j.colsurfb.2017.12.042 PMid:29287232

10. Elder A, Yang H, Gwiazda R, Teng X, Thurston S, He H, et al. Testing nanomaterials of unknown toxicity: An example based on platinum nanoparticles of different shapes. Adv Mater. 2007; 19:3124-29. https://doi.org/10.1002/adma.200701962

11. Kawasaki H, Yonezawa T, Watanable T, Arakawa R. Platinum nanoflowers for surface-assisted laser desorption / ionization mass spectrometry of biomolecules. J Phys Chem C. 2007; 111:16279-83. https://doi.org/10.1021/jp075159d

12. Johnstone TC, Suntharalingam K, Lippard SJ. The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chem Rev. 2016; 116(5):3436-86. https://doi.org/10.1021/acs.chemrev.5b00597 PMid:26865551 PMCid:PMC4792284

13. Wang Z, Chen L, Huang C, Huang Y, Jia N. Albumin-mediated platinum nanocrystals for in vivo enhanced computed tomography imaging. J Mater Chem B. 2017; 5(19):3498-510. https://doi.org/10.1039/C7TB00561J PMid:32264286

14. Testa G, Fontana L, Venditti I, Fratoddi I. Functionalized platinum nanoparticles with surface charge triggered by pH: Synthesis, characterization and stability studies. Beilstein J Nanotechnol. 2016; 7:1822-28. https://doi.org/10.3762/bjnano.7.175 PMid:28144532 PMCid:PMC5238631

15. Huang X, Jain PK, El-Sayed IH, El-Sayed MA. Goldnanoparticles: Interesting optical properties and recent applications in cancer diagnostics and therapy. Nanomed. 2007; 2(5):681-93. https://doi.org/10.2217/17435889.2.5.681 PMid:17976030

16. Yamada M, Foote M, Prow TW. Therapeutic gold, silver, and platinum nanoparticles. Wiley Interdiscip Rev: Nanomed Nanobiotechnol. 2015; 7:428-45. https://doi.org/10.1002/wnan.1322 PMid:25521618

17. Gao J, Liang G, Zhang B, Kuang Y, Zhang X, Xu B. FePt@CoS2 yolk-shell nanocrystals as a potent agent to kill HeLa cells. J Am Chem Soc. 2007; 129:1428-33. https://doi.org/10.1021/ja067785e PMid:17263428

18. Asharani P, Xinyi N, Hande MP, Valiyaveettil S. DNA damage and p53-mediated growth arrest in human cells treated with platinum nanoparticles. Nanomed. 2010; 5:51-64. https://doi.org/10.2217/nnm.09.85 PMid:20025464

19. Mony J, Ngamcherdtrakul W, Yantasee W. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox Biol. 2017; 11:240-53. https://doi.org/10.1016/j.redox.2016.12.011 PMid:28012439 PMCid:PMC5198743

20. Onizawa S, Aoshiba K, Kajita M, Miyamoto Y, Nagai A. Platinum nanoparticle antioxidants inhibit pulmonary inflammation in mice exposed to cigarette smoke. Pulm Pharmacol Ther. 2009; 22:340-49. https://doi.org/10.1016/j.pupt.2008.12.015 PMid:19166956

21. Pedone D, Moglianetti M, De Luca E, Bardi G, Pompa PP. Platinum nanoparticles in nanobiomedicine. Chem Soc Rev. 2017; 46:4951-75. https://doi.org/10.1039/C7CS00152E PMid:28696452

22. Mohammadi H, Abedi A, Akbarzadeh A, Mokhtari MJ, Shahmabadi HE, Mehrabi MR, et al. Evaluation of synthesized platinum nanoaprticles on the MCF-7 and HepG2 cancer cell lines. Int Nano Lett. 2013; 3:28. https://doi.org/10.1186/2228-5326-3-28

23. Liu Y, Wu HH, Li M, Yin JJ, Nie ZH. pH dependent catalytic activities of platinum nanoparticles with respect to the decomposition of hydrogen peroxide and scavenging of superoxide and singlet oxygen. Nanoscale. 2014; 6(20):11904-10. https://doi.org/10.1039/C4NR03848G PMid:25175625

24. Kumar PSM, Ponnusamy VK, Deepthi KR, Kumar G, Pugazhendhi A, Abe H, et al. Controlled synthesis of Pt nanoparticle supported TiO2 nanorods as efficient and stable electrocatalysts for the oxygen reduction reaction. J Mater Chem A. 2018; 6(46):23435-44. https://doi.org/10.1039/C8TA07380E

25. Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Abe K. Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice. Neuroscience. 2012; 221:47-55. https://doi.org/10.1016/j.neuroscience.2012.06.060 PMid:22766232

26. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci. 2002; 6:319-27. https://doi.org/10.1016/S1359-0286(02)00117-1

27. Rad JK, Alinejad Z, Khoei S, Mahdavian AR. Controlled release and photothermal behavior of multipurpose nanocomposite particles containing encapsulated gold-decorated magnetite and 5-FU in poly(lactide-co-glycolide). ACS Biomater Sci Eng. 2019; 5:4425-34. https://doi.org/10.1021/acsbiomaterials.9b00790 PMid:33438408

28. Danhier F, Ansorena E, Silva JM, Coco R, Breton AL, Preat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Rel. 2012; 161:505-22. https://doi.org/10.1016/j.jconrel.2012.01.043 PMid:22353619

29. Ramirez JC, Flores-VillaSenor SE, Vargas-Reyes E, Herrera-Ordonez J, Torres-Rincon S, Peralta-Rodriguez RD. Preparation of PDLLA and PLGA nanoparticles stabilized with PVA and PVA-SDS mixture: Studies on particle size, degradation and drug release. J Drug Deliv Sci Technol. 2020; 60:101907. https://doi.org/10.1016/j.jddst.2020.101907

30. Plch J, Venclikova K, Janouskova O, Hrabeta J, Eckschlager T, Kopeckova K, et al. Paclitaxel-loaded polylactide/polyethylene glycol fibers with long-term antitumor activity as a potential drug carrier for local chemotherapy. Macromol Biosci. 2018; 18:1800011. https://doi.org/10.1002/mabi.201800011 PMid:29688614

31. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science. 1994; 263:1600-3. https://doi.org/10.1126/science.8128245 PMid:8128245

32. Boulikas T, Pantos A, Bellis E, Christofis P. Designing platinum compounds in cancer: Structures and mechanisms. Cancer Ther. 2007; 5:537-83.

33. Watkins R, Wu L, Zhang C, Davis RM, Xu B. Natural product-based nanomedicine: Recent advances and issues. Int J Nanomed. 2015; 10:6055. https://doi.org/10.2147/IJN.S92162 PMid:26451111 PMCid:PMC4592057

34. Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, et al. Development of novel cationic chitosan- and anionic alginate- coated poly (D, L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol. Int J Nanomed. 2012; 7:5501. https://doi.org/10.2147/IJN.S36684 PMid:23093904 PMCid:PMC3477887

35. Kennedy PJ, Sousa F, Ferreira D, Pereira C, Nestor M, Oliveira C, et al. Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6. Acta Biomater. 2018; 81:208-18. https://doi.org/10.1016/j.actbio.2018.09.043 PMid:30267881

36. Fu B, Dang M, Tao J, Li Y, Tang Y. Mesoporous platinum nanoparticle-based nanoplatforms for combined chemo-photothermal breast cancer therapy. J Colloid Interf Sci. 2020; 570:197-204. https://doi.org/10.1016/j.jcis.2020.02.051 PMid:32151829

37. Oliveira BL, Stenton BJ, Unnikrishnan VB, deAlmeida CR, Conde J, Negrao M, et al. Platinum-triggered bond-cleavage of pentynoyl amide and N-propargyl handles for drug-activation. J Am Chem Soc. 2020; 142(24):10869-80. https://doi.org/10.1021/jacs.0c01622 PMid:32456416 PMCid:PMC7304066

38. Patel P, Nadar VM, Umapathy D, Manivannan S, Venkatesan R, Joseph-Arokiyam VA, et al. Doxorubicin-conjugated platinum theranostic nanoparticles induce apoptosis via inhibition of a cell survival (PI3K/AKT) signaling pathway in human breast cancer cells. ACS Appl Nano Mater. 2020; 4(1):198-210. https://doi.org/10.1021/acsanm.0c02521

39. Bahrami B, Hojjat-Farsangi M, Mohammadi H, Anvari E, Ghalamfarsa G, Yousefi M, et al. Nanoparticles and targeted drug delivery in cancer therapy. Immunol Lett. 2017; 190:64-83. https://doi.org/10.1016/j.imlet.2017.07.015 PMid:28760499

40. Zeng X, Sun J, Li S, Shi J, Gao H, Leong WS, et al. Blood-triggered generation of platinum nanoparticle functions as an anticancer agent. Nat Commun. 2020; 11(1):567. https://doi.org/10.1038/s41467-019-14131-z PMid:31992692 PMCid:PMC6987201

41. Aionb M, Panikkanvalappil SR, El-Sayed MA. Platinum-coated gold nanorods: Efficient reactive oxygen scavengers that prevent oxidative damage toward healthy, untreated cells during plasmonic photothermal therapy. ACS Nano. 2017; 11:579-86. https://doi.org/10.1021/acsnano.6b06651 PMid:28029783

42. Ataee-Esfahani H, Wang L, Nemoto Y, Yamauchi Y. Synthesis of bimetallic Au@Pt nanoparticles with Au core and nanostructured Pt shell toward highly active electrocatalysts. Chem Mater. 2010; 22(23):6310-18. https://doi.org/10.1021/cm102074w

43. He W, Liu Y, Yuan J, Yin JJ, Wu X, Hu X, et al. Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays. Biomater. 2011; 32(4):1139-47. https://doi.org/10.1016/j.biomaterials.2010.09.040 PMid:21071085

44. Li Y, Ding W, Li M, Xia H, Wang D, Tao X. Synthesis of core-shell Au-Pt nanodendrites with high catalytic performance via overgrowth of platinum on in situ gold nanoparticles. J Mater Chem A. 2015; 3(1):368-76. https://doi.org/10.1039/C4TA04940C

45. Liu X, Zhang X, Zhu M, Lin G, Liu J, Zhou Z, et al. PEGylated Au@Pt nanodendrites as novel theranostic agents for computed tomography imaging and photothermal / radiation synergistic therapy. ACS Appl Mater Interfaces. 2017; 9(1):279-85. https://doi.org/10.1021/acsami.6b15183 PMid:27966883

46. Shi Y, Lin M, Jiang X, Liang S. Recent advances in Fe-Pt nanoparticles for biomedicine. J Nanomater. 2015; 2015:467873. https://doi.org/10.1155/2015/467873

47. Chou SW, Shau YH, Wu PC, Yang YS, Shieh DB, Chen CC. In vitro and in vivo studies of Fe-Pt nanoparticles for dual model CT/MRI molecular imaging. J Am Chem Soc. 2010; 132(38):13270-78. https://doi.org/10.1021/ja1035013 PMid:20572667

48. Lai SM, Tsai TY, Hsu CY, Tsai JL, Liao MY, Lai PS. Bifunctional silica-coated super paramagnetic Fe-Pt nanoparticles for fluorescence/MR dual imaging. J Nanomater. 2012; 2012:5. https://doi.org/10.1155/2012/631584

49. Liang SY, Zhou Q, Wang M, Zhu Y, Wu Q, Yang XL. Water-soluble L-cysteine-coated Fe-Pt nanoparticles as dual MRI/CT imaging contrast agent for glioma. Int J Manomed. 2015; 10:2325-33. https://doi.org/10.2147/IJN.S75174 PMid:25848253 PMCid:PMC4376264

50. Fuchigami T, Kawamura R, Kitamoto Y, Nakagava M, Namiki Y. A magnetically guided anti-cancer drug delivery system using porous Fe-Pt capsules. Biomater. 2012; 33(5):1682-7. https://doi.org/10.1016/j.biomaterials.2011.11.016 PMid:22123601

51. Chen CL, Kuo LR, Lee SY, Hwu YK, Chou SW, Chen CC, et al. Photothermal cancer therapy via femtosecond-laser-excited Fe-Pt nanoparticles. Biomater. 2013; 34(4):1128-34. https://doi.org/10.1016/j.biomaterials.2012.10.044 PMid:23137396

52. Sun H, Chen X, Chen D, Dong M, Fu X, Li Q, et al. Influences of surface coatings and components of Fe-Pt nanoparticles on the suppression of glioma cell proliferation. Int J Nanomed. 2012; 7:3295-307. https://doi.org/10.2147/IJN.S32678 PMid:22848161 PMCid:PMC3405879

53. Zheng Y, Tang Y, Bao Z, Wang H, Ren F, Guo M, et al. Fe-Pt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells. Int J Nanomed. 2015; 10:6435-44. https://doi.org/10.2147/IJN.S88458 PMid:26604740 PMCid:PMC4629968

54. Tseng CL, Chang KC, Yeh MC, Yang KC, Tang TP, Lin FH. Development of a dual-functional Pt-Fe-HAP magnetic nanoparticles application for chemo-hyperthermia treatment of cancer. Ceramics Int. 2014; 40(4):5117-27. https://doi.org/10.1016/j.ceramint.2013.09.137

55. Jeyaraj M, Gurunathan S, Qasim M, Kang MH, Kim JH. A comprehensive review on the synthesis, characterization, and biomedical application of platinum nanoparticles. Nanomater(Basel).2019; 9(12):1719. https://doi.org/10.3390/nano9121719 PMid:31810256 PMCid:PMC6956027

56. Shim K, Kim J, Heo YU, Jiang B, Li C, Shahabuddin M, et al. Synthesis and cytotoxicity of dendritic platinum nanoparticles with HEK-293 cells. Chem Asian J. 2017; 12:21-6. https://doi.org/10.1002/asia.201601239 PMid:27911052

57. Chen S, Kimura K. Synthesis of thiolate-stabilized platinum nanoparticles in protolytic solvents as isolable colloids. J Physic Chem B. 2001; 105(23):5397-403. https://doi.org/10.1021/jp0037798

58. Islam MT, Saenz-Arana R, Wang H, Bernal R, Noveron JC. Green synthesis of gold, silver, platinum, and palladium nanoparticles reduced and stabilized by sodium rhodizonate and their catalytic reduction of 4-nitrophenol and methyl orange. New J Chem. 2018; 42:6472-8. https://doi.org/10.1039/C8NJ01223G

59. Gao Z, Ye H, Tang D, Tao J, Habibi S, Minerick A, et al. Platinum-decorated gold nanoparticles with dual functionalities for ultrasensitive colorimetric in vitro diagnostics. Nano Lett. 2017; 17(9):5572-9. https://doi.org/10.1021/acs.nanolett.7b02385 PMid:28813601

60. Sivaraman SK, Kumar S, Santhanam V. Monodisperse sub 10 nm gold nanoparticles by reversing the order of addition in Turkevich method-the role of chloroauric acid. J Colloid Interface Sci. 2011; 361:543-7. https://doi.org/10.1016/j.jcis.2011.06.015 PMid:21719021

61. Theodosiou M, Boukos N, Sakellis E, Zachariadis M, Efthimiadou ER. Gold nanoparticle decorated pH-sensitive polymeric nanocontainers as a potential theranostic agent. Colloids Surf B: Biointerfaces. 2019; 183:110420. https://doi.org/10.1016/j.colsurfb.2019.110420 PMid:31421401

62. Low A, Bansal V. A visual tutorial on the synthesis of gold nanoparticles. Biomed Imaging Interv J. 2010; 6:e9. https://doi.org/10.2349/biij.6.1.e9 PMid:21611068 PMCid:PMC3097789

63. La Spina R, Spampinato V, Gilliland D, Ojea-Jimenez I, Ceccone G. Influence of different cleaning processes on the surface chemistry of gold nanoparticles. Biointerphases. 2017; 12:031003. https://doi.org/10.1116/1.4994286 PMid:28750541

64. Ojea-Jimenez I, Campanera JM. Molecular modeling of the reduction mechanism in the citrate-mediated synthesis of gold nanoparticles. J Phys Chem C. 2012; 116:23682-91. https://doi.org/10.1021/jp305830p

65. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3):209-49. https://doi.org/10.3322/caac.21660 PMid:33538338

66. Song JY, Kwon EY, Kim BS. Biological synthesis of platinum nanoparticles using Diopyros kaki leaf extract. Bioprocess Biosyst Eng. 2010; 33:159-64. https://doi.org/10.1007/s00449-009-0373-2 PMid:19701776

67. Dobrucka R. Synthesis and structural characteristic of platinum nanoparticles using herbal Bidens tripartitus extract. J Inorg Organomet Polym Mater. 2015; 26:219-25. https://doi.org/10.1007/s10904-015-0305-3

68. Sheny DS, Philip D, Mathew J. Synthesis of platinum nanoparticles using dried Anacardium occidentale leaf and its catalytic and thermal applications. Spectrochim Acta A Mol Biomol Spectrosc. 2013; 114:267-71. https://doi.org/10.1016/j.saa.2013.05.028 PMid:23786970

69. Thirumurugan A, Aswitha P, Kiruthika C, Nagarajan S, Nancy CA. Green synthesis of platinum nanoparticles using Azadirachta indica - An eco-frinedly approach. Mater Lett. 2016; 170:175-8. https://doi.org/10.1016/j.matlet.2016.02.026

70. Rajasekharreddy P, Rani PU. Biosynthesis and characterization of Pd and Pt nanoparticles using Piper betle L. plant in a photoreduction method. J Cluster Sci. 2014; 25:1377-88. https://doi.org/10.1007/s10876-014-0715-3

71. Soundarrajan C, Sankari A, Dhandapani P, Maruthamuthu S, Ravichandran S, Sozhan G, et al. Rapid biological synthesis of platinum nanoparticles using OcimumSanctum for water electrolysis applications. Bioprocess Biosyst Eng. 2012; 35:827-33. https://doi.org/10.1007/s00449-011-0666-0 PMid:22167464

72. Huang J, Li Q, Sun D, Lu Y, Su Y, Yang X, et al. Biosynthesis of silver and gold nanoparticles by novel sun dried Cinnamomum camphora leaf. Nanotechnol. 2007; 18:105104-14. https://doi.org/10.1088/0957-4484/18/10/105104

73. Mahmoudi M, Sant S, Wang B, Laurent S, Sen T. Super-paramagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev. 2011; 63(1-2):24-26. https://doi.org/10.1016/j.addr.2010.05.006 PMid:20685224

74. Li L, Jiang W, Luo K, Song H, Lan F, Wu Y, et al. Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics. 2013; 3(8):595-615. https://doi.org/10.7150/thno.5366 PMid:23946825 PMCid:PMC3741608

75. Amstad E, Textor M, Reimhult E. Stabilization and functionalization of iron oxide nanoparticles for biomedical applications. Nanoscale. 2011; 3(7):2819-43. https://doi.org/10.1039/c1nr10173k PMid:21629911

76. Xu C, Sun S. Superparamagnetic nanoparticles as targeted probes for diagnostic and therapeutic applications. Dalton Transactions. 2009; 29:5583-91. https://doi.org/10.1039/b900272n PMid:20449070 PMCid:PMC2867062

77. Chen H, Wang L, Yu Q, Qian W, Tiwari D, Yi H, et al. Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer. Int J Nanomed. 2013; 8:3781-94. https://doi.org/10.2147/IJN.S49069 PMid:24124366 PMCid:PMC3794963

78. Cardoso MM, Peca IN, Roque ACA. Antibody-conjugated nanoparticles for therapeutic applications. Curr Med Chem. 2012; 19:3103-27. https://doi.org/10.2174/092986712800784667 PMid:22612698

79. Rai M, Ingle AP, Birla S, Yadav A, DosSantos CA. Strategic role of selected noble metal nanoparticles in medicine. Crit Rev Microbiol. 2016; 42:696-719.

80. Fatima S, Iqbal Z, Panda AK, Samim M, Talegaonkar S, Ahmad FJ. Polymeric nanoparticles as a platform for permeability enhancement of class III drug amikacin. Colloids Surf B. 2018; 169:206-13. https://doi.org/10.1016/j.colsurfb.2018.05.028 PMid:29778036

81. Ben-Nissan B, Choi AH. Sol-gel production of bioactive nanocoatings for medical applications: Part I: An introduction. Nanomed. 2006; 1:311-19. https://doi.org/10.2217/17435889.1.3.311 PMid:17716161

82. Minati L, Antonini V, DallaSerra M, Speranza G. Multifunctional branched gold-carbon nanotube hybrid for cell imaging and drug delivery. Langmuir. 2012; 28(45):15900-6. https://doi.org/10.1021/la303298u PMid:23083447

83. Manson J, Kumar D, Meenan BJ, Dixon D. Polyethylene glycol functionalized gold nanoparticles: The influence of capping density on stability in various media. Gold Bull. 2011; 44(2):99-105. https://doi.org/10.1007/s13404-011-0015-8

84. Tanaka Y, Maenosono S. Amine-terminated water dispersible FePt nanoparticles. J Magnet Magnetic Mater. 2008; 320(19):L121-4. https://doi.org/10.1016/j.jmmm.2008.05.011

85. Maenosono S, Yoshida R, Saita S. Evaluation of genotoxicity of amine-terminated water-dispersible FePt nanoparticles in the Ames test and in vitro chromosomal aberration test. J Toxicol Sci. 2009; 34(3):349-54. https://doi.org/10.2131/jts.34.349 PMid:19483389

86. Chen S, Wang L, Duce SL, Brown S, Lee S, Melzer A, et al. Engineered biocompatible nanoparticles for in vivo imaging applications. J Am Chem Soc. 2010; 132(42):15022-9. https://doi.org/10.1021/ja106543j PMid:20919679 PMCid:PMC2962530

87. Yang H, Zhang J, Tian Q, Hu H, Fang Y, Wu H, et al. One-pot synthesis of amphiphilic superparamagnetic FePt nanoparticles and magnetic resonance imaging in vitro. J magnet Magnetic Mater. 2010; 322(8):937-77. https://doi.org/10.1016/j.jmmm.2009.11.039

88. Fuchigami T, Kawamura R, Kitamoto Y, Nakagawa M, Namiki Y. Ferromagnetic FePt-nanoparticles / polycation hybrid capsules designed for a magnetically guided drug delivery system. Langmuir. 2011; 27(6):2923-8. https://doi.org/10.1021/la1041019 PMid:21291255

89. Hariri G, Wellons MS, MorrisIII WH, Lukehart CM, Hallahan DE. Multifunctional mFePt nanoparticles for radiation-guided targeting and imaging of cancer. Ann Biomed Eng. 2011; 39(3):946-52. https://doi.org/10.1007/s10439-010-0219-8 PMid:21132370 PMCid:PMC4401085

90. Liu Y, Yang K, Cheng L, Xhu J, Ma X, Xu H, et al. PEGylated FePt@Fe₂O₃ coreshell magnetic nanoparticles: Potential therapeutic applications and in vivo toxicity studies. Nanomed: Nanotechnol Biol Med. 2013; 9(7):1077-88. https://doi.org/10.1016/j.nano.2013.02.010 PMid:23499668

91. Yang Q, Pang J, Xiao Y, Li W, Tan L, Xu X, et al. Porous Au@Pt nanoparticles: Therapeutic platform for tumor chemo-photothermal co-therapy and alleviating doxorubicin-induced oxidative damage. ACS Appl Mater Interfaces. 2018; 10:150-64. https://doi.org/10.1021/acsami.7b14705 PMid:29251910

92. Zhao HY, Liu S, He J, Pan CC, Li H, Zhou ZY, et al. Synthesis and application of strawberry-like Fe₃O₄-Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease. Biomater. 2015; 51:194-207. https://doi.org/10.1016/j.biomaterials.2015.02.019 PMid:25771010

93. Tahir K, Nazir S, Ahmad A, Li B, Khan AU, Khan ZUH, et al. Facile and green synthesis of phytochemicals capped platinum nanoparticles and in vitro their superior anti-bacterial activity. J Phytochem Photobiol B. 2017; 166:246-51. https://doi.org/10.1016/j.jphotobiol.2016.12.016 PMid:28011434

94. Akther T, Khan MS, Srinivasan H. Novel silver nanoparticles synthesized from anthers of Couroupitaguianensisabul. Control growth and biofilm formation in human pathogenic bacteria. Nano Biomed Eng. 2018; 10(3):250-7. https://doi.org/10.5101/nbe.v10i3.p250-257

95. Gehrke H, Pelka J, Hartinger CG, Blank H, Bleimund F, Schneider R, et al. Platinumm nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations. Arch Toxicol. 2011; 85(7):799-812. https://doi.org/10.1007/s00204-010-0636-3 PMid:21229235

96. Almeer RS, Ali D, Alarifi S, Alkahtani S, Almansour M. Green platinum nanoparticles interaction with HEK293 cells: Cellular toxicity, apoptosis, and genetic damage. Dose-Response. 2018; 16(4):155932581880738. https://doi.org/10.1177/1559325818807382 PMid:30479585 PMCid:PMC6247496

97. Zhang Y, Yuan J, Zhang HY, Simayi D, Li PD, Wang YH, et al. Natural resistance to apoptosis correlates with resistance to chemotherapy in colorectal cancer cells. Clinic Expt Med. 2011; 12(2):97-103. https://doi.org/10.1007/s10238-011-0146-5 PMid:21688119

98. Gillet JP, Gottesman MM. Mechanisms of multidrug resistance in cancer. Method Mol Biol:Human Press. 2009; p. 47-76. https://doi.org/10.1007/978-1-60761-416-6_4 PMid:19949920

99. Su L, Gong X, Fan R, Ni T, Yang F, Zhang X, et al. Mechanism of action of platinum nanoparticles implying from antioxidant to metabolic programming in light-induced retinal degeneration model. Redox Biol. 2023; 65:102836. https://doi.org/10.1016/j.redox.2023.102836 PMid:37541055 PMCid:PMC10412868

100. Gurunathan S, Jeyaraj M, Kang MH, Kim JH. Anticancer properties of platinum nanoparticles and retinoic acid: Combination therapy for the treatment of human neuroblastoma cancer. Int J Mol Sci. 2020; 21(18):6792. https://doi.org/10.3390/ijms21186792 PMid:32947930 PMCid:PMC7554966

101. Lopez Ruiz A, Bartomeu Garcia C, Navarro Gallon S, Webster TJ. Novel silver-platinum nanoparticles for anticancer and antimicrobial applications. Int J Nanomed. 2020; 15:169-79. https://doi.org/10.2147/IJN.S176737 PMid:32021172 PMCid:PMC6970512

102. Manikandan M, Hasan N, Wu HF. Platinum nanoparticles for the photothermal treatment of Neuro 2A cancer cells. Biomater. 2013; 34(23):5833-42. https://doi.org/10.1016/j.biomaterials.2013.03.077 PMid:23642996

103. Armada-Moreira A, Taipaleenmaki E, Backgaard-Laursen M, Schattling PS, Sebastiao AM, Vaz SH, et al. Platinum nanoparticle-based microreactors as support for neuroblastoma cells. ACS Appl Mater Inter. 2017; 10(9):7581-92. https://doi.org/10.1021/acsami.7b10724 PMid:29083859

104. Setua S, Ouberai M, Piccirillo SG, Watts C, Welland M. Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma. Nanoscale. 2014; 6(18):10865-73. https://doi.org/10.1039/C4NR03693J PMid:25117686

105. Lopez T, Figueras F, Manjarrez J, Bustos J, Alvarez M, Silvestre-Albero J, et al. Catalytic nanomedicine: A new field in antitumor treatment using supported platinum nanoparticles. In vitro DNA degradation and in vivo tests with C6 animal model on Wistar rats. Eur J Med Chem. 2010; 45(5):1982-90. https://doi.org/10.1016/j.ejmech.2010.01.043 PMid:20153564

106. Aygun A, Gulbagca F, Ozer LY, Ustaoglu B, Altunoglu YC, Baloglu MC, et al. Biogenetic platinum nanoparticles using black cumin seed and their potential usage as antimicrobial and anticancer agent. J Pharm Biomed Anal. 2020; 179:112961. https://doi.org/10.1016/j.jpba.2019.112961 PMid:31732404

107. Gu T, Wang Y, Lu Y, Cheng L, Feng L, Zhang H, et al. Platinum nanoparticles to enable electrodynamic therapy for effective cancer treatment. Adv Mater. 2019; 31(14):e1806803. https://doi.org/10.1002/adma.201806803 PMid:30734370

108. Baskaran B, Muthukumarasamy A, Chidambaram S, Sugumaran A, Ramachandran K, RasuManimuthu T. Cytotoxic potentials of biologically fabricated platinum nanoparticles from Streptomyces sp. on MCF-7 breast cancer cells. IET Nanobiotechnol. 2017; 11(3):241-6. https://doi.org/10.1049/iet-nbt.2016.0040 PMid:28476980 PMCid:PMC8676093

109. Teow Y, Valiyaveettil S. Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles. Nanoscale. 2010; 2:2607-13. https://doi.org/10.1039/c0nr00204f PMid:20936240

110. Wawrowicz K, Majkowska-Pilip A, Gawel D, Chajduk E, Pienkowski T, Bilewicz A. Au@Pt core-shell nanoparticle bioconjugates for the therapy of HER2+ breast cancer and hepatocellular carcinoma. Model studies on the applicability of 193mPt and 195mPt radionuclides in Auger electron therapy. Molecules. 2021; 26(7):2051. https://doi.org/10.3390/molecules26072051 PMid:33916671 PMCid:PMC8038409

111. Kim MI, Kim MS, Woo MA, Ye Y, Kang KS, Lee J, et al. Highly efficient colorimetric detection of target cancer cells utilizing superior catalytic activity of graphene oxide-magnetic-platinum nanohybrids. Nanoscale. 2014; 6(3):1529-36. https://doi.org/10.1039/C3NR05539F PMid:24322602

112. Paraskar AS, Soni S, Chin KT, Chaudhuri P, Muto KW, Berkowitz J, et al. Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy. Proc Natl Acad Sci USA. 2010; 107(28):12435-40. https://doi.org/10.1073/pnas.1007026107 PMid:20616005 PMCid:PMC2906605

113. Paraskar A, Soni S, Basu S, Amarasiriwardena CJ, Lupoli N, Srivats S, et al. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy. Nanotechnol. 2011; 22(26):265101. https://doi.org/10.1088/0957-4484/22/26/265101 PMid:21576779 PMCid:PMC3158969

114. Ma Y, Zhang DY, Peng Z, Guan S, Zhai J. Delivery of platinum(IV) prodrugs via Bi2Te3 nanoparticles for photothermal chemotherapy and photothermal / photoacoustic imaging. Mol Pharm. 2020; 17(9):3403-11. https://doi.org/10.1021/acs.molpharmaceut.0c00458 PMid:32692573

115. Ding F, Zhang L, Chen H, Song H, Chen S, Xiao H. Enhancing the chemotherapeutic efficacy of platinum prodrug nanoparticles and inhibiting cancer metastasis by targeting iron homeostasis. Nanoscale Horiz. 2020; 5(6):999-1015. https://doi.org/10.1039/D0NH00148A PMid:32364553

116. Yang X, Salado-Leza D, Porcel E, Vargas-Gonzalez CR, Savina F, Dragoe D, et al. A facile one-pot synthesis of versatile PEGylated platinum nanoflowers and their application in radiation therapy. Int J Mol Sci. 2020; 21:1619. https://doi.org/10.3390/ijms21051619 PMid:32120829 PMCid:PMC7084439

117. Alshatwi AA, Athinarayanan J, Vaiyapuri Subbarayan P. Green synthesis of platinum nanoparticles that induce cell death and G2/M-phase cell cycle arrest in human cervical cancer cells. J Mater Sci Mater Med. 2015; 26(1):5330. https://doi.org/10.1007/s10856-014-5330-1 PMid:25577212

118. Guarnieri D, Melone P, Moglianetti M, Marotta R, Netti PA, Pompa PP. Particle size affects the cytosolic delivery of membranotropic peptide-functionalized platinum nanozymes. Nanoscale. 2017; 9:11288-96. https://doi.org/10.1039/C7NR02350B PMid:28758654

119. Medhat A, Mansour S, El-Sonbaty S, Kandil E, Mahmoud M. Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats. Tumor Biol. 2017; 39(7):1010428317717259. https://doi.org/10.1177/1010428317717259 PMid:28720064

120. Almarzoug MHA, Ali D, Alarifi S, Alkahtani S, Alhadheq AM. Platinum nanoparticles induced genotoxicity and apoptotic activity in human normal and cancer hepatic cells via oxidative stress-mediated Bax/Bcl-2 and caspase-3 expression. Environ Toxicol. 2020; 35(9):930-41. https://doi.org/10.1002/tox.22929 PMid:32309901

121. Bendale Y, Bendale V, Paul S. Evaluation of cytotoxic activity of platinum nanoparticles against normal and cancer cells and its anticancer potential through induction of apoptosis. Integr Med Res. 2017; 6:141-8. https://doi.org/10.1016/j.imr.2017.01.006 PMid:28664137 PMCid:PMC5478255

122. Feldmann DP, Heyza J, Zimmermann CM, Patrik SM, Merkel OM. Nanoparticle-mediated gene silencing for sensitization of lung cancer to cisplatin therapy. Molecules. 2020; 25(8):1994. https://doi.org/10.3390/molecules25081994 PMid:32344513 PMCid:PMC7221615

123. Li Y, Yun KH, Lee H, Goh SH, Suh YG, Choi Y. Porous platinum nanoparticles as a high-z and oxygen generating nanozyme for enhanced radiotherapy in vivo. Biomater. 2019; 197:12-19. https://doi.org/10.1016/j.biomaterials.2019.01.004 PMid:30623793

124. Dobrucka R, Romaniuk-Drapala A, Kaczmarck M. Evaluation of biological synthesized platinum nanoparticles using Ononidis radix extract on the cell lung carcinoma A549. Biomed Microdevices. 2019; 21(3):75. https://doi.org/10.1007/s10544-019-0424-7 PMid:31346766 PMCid:PMC6658583

125. Ullah S, Ahmad A,Wang A, Raza M, Jan AU, Tahir K, et al. Biofabrication of catalytic platinum nanoparticles and their in vitro efficacy against lungs cancer cells line (A549). J Photochem Photobiol B. 2017; 173:368-75. https://doi.org/10.1016/j.jphotobiol.2017.06.018 PMid:28646755

126. Jia YY, Zhang JJ, Zhang YX, Wang W, Li C, Zhou SY, et al. Construction of redox-responsive tumor targeted cisplatin nano-delivery system for effective cancer chemotherapy. Int J Pharm. 2020; 580:119190. https://doi.org/10.1016/j.ijpharm.2020.119190 PMid:32151664

127. Sun Y, Miao H, Ma S, Zhang L, You C, Tang F, et al. FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro. Cancer Lett. 2018; 418:27-40. https://doi.org/10.1016/j.canlet.2018.01.024 PMid:29331422

128. Yogesh B, Vineeta B, Rammesh N, Saili P. Biosynthesized platinum nanoparticles inhibit the proliferation of human lung cancer cells in vitro and delay the growth of a human lung tumor xenograft in vivo. J Pharmacopunct. 2016; 19(2):114-21. https://doi.org/10.3831/KPI.2016.19.012 PMid:27386144 PMCid:PMC4931296

129. Yang YT, Shi Y, Jay M, Di Pasqua AJ. Enhanced toxicity of cisplatin with chemosensitizer phenethyl isothiocyanate toward non-small cell lung cancer cells when delivered in liposomal nanoparticles. Chem Res Toxicol. 2014; 27(6):946-8. https://doi.org/10.1021/tx5001128 PMid:24836554

130. Sadhukha T, Prabha S. Encapsulation in nanoparticles improves anti-cancer efficacy of carboplatin. Aaps Pharm Sci Tech. 2014; 15(4):1029-38. https://doi.org/10.1208/s12249-014-0139-2 PMid:24831091 PMCid:PMC4113618

131. Gurunathan S, Kang MH, Jeyaraj M, Kim JH. Platinum nanoparticles enhance exosome release in human lung epithelial adenocarcinoma cancer cells (A549): Oxidative stress and the ceramide pathway are key players. Int J Nanomed. 2021; 16:515-38. https://doi.org/10.2147/IJN.S291138 PMid:33519199 PMCid:PMC7837572

132. Pelka J, Gehrke H, Esselen M, Turk M, Crone M, Brase S, et al. Cellular uptake of platinum nanoparticles in human colon carcinoma cells and their impact on cellular redox systems and DNA integrity. Chem Res Toxicol. 2009; 22(4):649-59. https://doi.org/10.1021/tx800354g PMid:19290672

133. Blank H, Schneider R, Gerthsen D, Gehrke H, Jarolim K, Marko D. Application of low-energy scanning transmission electron microscopy for the study of Pt-nanoparticle uptake in human colon carcinoma cells. Nanotoxicol. 2014; 8(4):433-46. https://doi.org/10.3109/17435390.2013.796535  PMid:23590554

134. Chaturvedi VK, Yadav N, Rai NK, Bohara RA, Rai SN, Aleya L, et al. Two birds with one stone: Oyster mushroom mediated bimetallic Au-Pt nanoparticles for agro-waste management and anticancer activity. Environ Sci Pollut Res Int. 2021; 28(11):13761-75. https://doi.org/10.1007/s11356-020-11435-2 PMid:33196993

135. Klebowski B, Depciuch J, Stec M, Krzempek D, Komenda W, Baran J, et al. Fancy-shaped gold-platinum nanocauliflowers for improved proton irradiation effect on colon cancer cells. Int J mol Sci. 2020; 21(24):9610. https://doi.org/10.3390/ijms21249610 PMid:33348549 PMCid:PMC7766784

136. Al-Fahdawi MQ, Al-Doghachi FAJ, Abdullah QK, Hammad RT, Rasedee A, Ibrahim WN, et al. Oxidative stress cytotoxicity induced by platinum-doped magnesia nanoparticles in cancer cells. Biomed Pharmacother. 2021; 138:111483. https://doi.org/10.1016/j.biopha.2021.111483 PMid:33744756

137. Samadi A, Klingberg H, Jauffred L, Kjaer A, Bendix PM, Oddershede LB. Platinum nanoparticles: A non-toxic, effective and thermally stable alternative plasmonic material for cancer therapy and bioengineering. Nanoscale. 2018; 10(19):9097-107. https://doi.org/10.1039/C8NR02275E PMid:29718060

138. Sanchez-Ramirez DR, Dominguez-Rios R, Juarez J, Valdes M, Hassan N, Quintero-Ramos A, et al. Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer. Mater Sci Eng C. 2020; 116:111196. https://doi.org/10.1016/j.msec.2020.111196 PMid:32806317

139. Zhang C, Zhao X, Guo H. Synergic highly effective photothermal chemotherapy with platinum prodrug linked melanin-like nanoparticles. Artif Cell Nanomed Biotechnol. 2018; 46(Suppl 2): 356-63. https://doi.org/10.1080/21691401.2018.1457536 PMid:29607699

140. Bortot B, Mongiat M, Valencic E, Dal Monego S, Licastro D, Crosera M, et al. Nanotechnology-based cisplatin intracellular delivery to enhance chemo-sensitivity of ovarian cancer. Int J Nanomed. 2020; 15:4793-810. https://doi.org/10.2147/IJN.S247114 PMid:32764921 PMCid:PMC7368240

141. Xu C, Yuan Z, Kohler N, Kim J, Chung MA, Sun S. FePt nanoparticles as a Fe reservoir for controlled Fe release and tumor inhibition. J Am Chem Soc. 2009; 131(42):15346-51. https://doi.org/10.1021/ja905938a PMid:19795861 PMCid:PMC2791709

142. Turiel-Fernandez D, Gutierrez-Romero L, Corte-Rodriguez M, Bethmer J, Montes-Bayon M. Ultra-small iron oxide nanoparticles cisplatin(IV) prodrug nanoconjugate: ICP-MS based strategies to evaluate the formation and drug delivery capabilities inn single cells. Analytica Chim Acta. 2021; 1159:338356. https://doi.org/10.1016/j.aca.2021.338356 PMid:33867043

143. Wang H, Qiu Z, Liu H, Jayawardhana AMDS, Yue Z, Dsghlas H, et al. Nanoparticles of metal-organic cages overcoming drug resistance in ovarian cancer. Front Chem. 2019; 7:39. https://doi.org/10.3389/fchem.2019.00039 PMid:30775364 PMCid:PMC6367237

144. Shin SS, Noh DH, Hwang B, Lee JW, Park SL, Park SS, et al. Inhibitory effect of Au@Pt-NSs on proliferation, migration and invasion of EJ bladder carcinoma cells: Involvement of cell cycle regulators, signaling pathways, and transcription factor-mediated MMP-9 expression. Int J Nanomed. 2018; 13:3295-310. https://doi.org/10.2147/IJN.S158463 PMid:29910616 PMCid:PMC5987858

145. Ma H, Zhang X, Li X, Li R, Du B, Wei Q. Electrochemical immunosensor for detecting typical bladder cancer biomarker based on reduced graphene oxide-tetraethylene pentamine and trimetallic AuPdPt nanoparticles. Talanta. 2015; 143:77-82. https://doi.org/10.1016/j.talanta.2015.05.029 PMid:26078131

146. Zhang M, Hagan CT, Min Y, Foley H, Tian X, Yang F, et al. Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models. Biomater. 2018; 169:1-10. https://doi.org/10.1016/j.biomaterials.2018.03.055 PMid:29631163 PMCid:PMC5911411

147. Gusti-Ngurah-Putu EP, Huang L, Hsu YC. Effective combined photodynamic therapy with lipid platinum chloride nanoparticles therapies of oral squamous carcinoma tumor inhibition. J Clin Med. 2019; 8(12):2112. https://doi.org/10.3390/jcm8122112 PMid:31810241 PMCid:PMC6947167

148. Gurunathan S, Jeyaraj M, Kang MH, Kim JH. Tangeretin-assisted platinum nanoparticles enhance the apoptotic properties of doxorubicin: Combination therapy for osteosarcoma treatment. Nanomater (Basel). 2019; 9(8):1089. https://doi.org/10.3390/nano9081089 PMid:31362420 PMCid:PMC6723885

149. Jawaid P, Rehman MU, Hassan MA, Zhao QL, Li P, Miyamoto Y, et al. Effect of platinum nanoparticles on cell death induced by ultrasound in human lymphoma U937 cells. Ultrason Sonochem. 2016; 31:206-15. https://doi.org/10.1016/j.ultsonch.2015.12.013 PMid:26964942

150. Yoshihisa Y, Zhao QL, Hassan MA, Wei ZL, Furuichi M, Miyamoto Y, et al. SOD/catalase mimetic platinum nanoparticles inhibit heat-induced apoptosis in human lymphoma U937 and HH cells. Free Radic Res. 2011; 45(3):326-35. https://doi.org/10.3109/10715762.2010.532494 PMid:21047173

151. Daneshvar F, Salehi F, Karini M, Vais RD, Mosleh-Shirazi MA, Sattarahmady N. Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles. J Photochem Photobiol B. 2020; 203:111737. https://doi.org/10.1016/j.jphotobiol.2019.111737 PMid:31862636

152. Gurunathan S, Jeyaraj M, La H, Yoo H, Choi Y, Do JT, et al. Anisotropic platinum nanoparticle-induced cytotoxicity, apoptosis, inflammatory response, and transcriptomic and molecular pathways in human acute monocytic leukemia cells. Int J Mol Sci. 2020; 21(2): 440. https://doi.org/10.3390/ijms21020440 PMid:31936679 PMCid:PMC7014054

153. Ramkumar VS, Pugazhendhi A, Prakash S, Ahila NK, Vinoj G, Selvam S, et al. Synthesis of platinum nanoparticles using seaweed Padina gymnospora and their catalytic activity as PVP/PtNPs nanocomposite towards biological applications. Biomed Pharmacother. 2017; 92:479-90. https://doi.org/10.1016/j.biopha.2017.05.076 PMid:28570982

154. Madlum KN, Khamoos EJ, Abdulridha SA, Naji RA. Antimicrobial and cytotoxic activity of platinum nanoparticles synthesized by laser ablation technique. J Nanostruct. 2021; 11(1):13-19.

155. Zhu S, Zeng M, Feng G, Wu H. Platinum nanoparticles as a therapeutic agent against dextran sodium sulfate-induced colitis in mice. Int J Nanomed. 2019; 14:8361-78. https://doi.org/10.2147/IJN.S210655 PMid:31749615 PMCid:PMC6804678

156. Stavropoulou AP, Theodosiou M, Sakellis E, Boukos N, Papanastasiou G, Wang C, et al. Bimetallic gold-platinum nanoparticles as a drug delivery system coated with a new drug to target glioblastoma. Colloi Surf B Biointerf. 2022; 214:112463. https://doi.org/10.1016/j.colsurfb.2022.112463 PMid:35316703

157. Depciuch J, Stec M, Klebowski B, Baran J, Parlinska-Wajtan M. Platinum-gold nanoraspberries as effective photosensitizer in anticancer photothermal therapy. J Nanobiotechnol. 2019; 17(1):107-12. https://doi.org/10.1186/s12951-019-0539-2 PMid:31615520 PMCid:PMC6794780

158. Chen Y, Wang J, Wang J, Wang L, Tan X, Tu K, et al. Aptamer functionalized cisplatin-albumin nanoparticles for targeted delivery to epidermal growth factor receptor positive cervical cancer. J Biomed Nanotechnol. 2016; 12(4):656-66. https://doi.org/10.1166/jbn.2016.2203 PMid:27301192

159. Kang S, Kang K, Chae A, Kim YK, Jang H, Min DH. Fucoidan-coated coral-like Pt nanoparticles for computed tomography-guided highly enhanced synergistic anticancer effect against drug-resistant breast cancer cells. Nanoscale. 2019; 11(32):15173-83. https://doi.org/10.1039/C9NR04495G PMid:31380881

160. Kutwin M, Sawosz E, Jaworski S, Wierzbicki M, Strojny B, Grodzik M, et al. Nanocomplexes of graphene oxide and platinum nanoparticles against colorectal cancer colo205, HT-29, HTC-116, SW-480, liver cancer HepG2, human breast cancer MCF-7, and adenocarcinoma LNCaP and human cervical HeLa cell lines. Mater (Basel). 2019; 12(6):909. https://doi.org/10.3390/ma12060909 PMid:30893818 PMCid:PMC6470683

161. Paraskar A, Soni S, Roy B, Papa AL, Sengupta S. Rationally designed oxaliplatin-nanoparticle for enhanced antitumor efficacy. Nanotechnol. 2012; 23(7):075103. https://doi.org/10.1088/0957-4484/23/7/075103 PMid:22275055 PMCid:PMC3387556

162. Patel P, Umapathy D, Manivannan S, Nadar VM, Venkatesan R, Arokiyam VAJ, et al. A doxorubicin-platinum conjugate system: Impacts on PI3K/AKT actuation and apoptosis in breast cancer cells. RSC Adv. 2021; 11:4818-28. https://doi.org/10.1039/D0RA06708C PMid:35424411 PMCid:PMC8694461

163. Kankala RK, Liu CG, Yang DY, Wang SB, Chen AZ. Ultrasmall platinum nanoparticles enable deep tumor penetration and synergistic therapeutic abilities through free radical species-assisted catalysis to combat cancer multi drug resistance. Chem Eng J. 2020; 383:123138. https://doi.org/10.1016/j.cej.2019.123138

164. Dhavale RP, Dhavale RP, Sahoo SC, Kollu P, Jadhav SU, Patil PS, et al. Chitosan coated magnetic nanoparticles as carriers of anticancer drug telmisartan: pH-responsive controlled drug release and cytotoxicity studies. J Phys Chem Solids. 2021; 148:109749. https://doi.org/10.1016/j.jpcs.2020.109749

165. Quarta A, Amorin M, Aldegunde MJ, Blasi L, Ragusa A, Nitti S, et al. Novel synthesis of platinum complexes and their intracellular delivery to tumor cells by means of magnetic nanoparticles. Nanoscale. 2019; 11(48):23482-97. https://doi.org/10.1039/C9NR07015J PMid:31808496

166. Shoshan MS, Vonderach T, Hattendorf B, Wennemers H. Peptide-coated platinum nanoparticles with selective toxicity against liver cancer cells. Angew Chem Int Ed Engl. 2019; 58(15):4901-5. https://doi.org/10.1002/anie.201813149 PMid:30561882

167. Wang X, Chang Z, Nie X, Li Y, Hu Z, Ma J, et al. A conveniently synthesized Pt(IV) conjugated alginate nanoparticle with ligand self-shield properly for targeting treatment of hepatic carcinoma. Nanomed. 2019; 15(1):153-63. https://doi.org/10.1016/j.nano.2018.09.012 PMid:30308299

168. Tsai HI, Jiang L, Zeng X, Chen H, Li Z, Cheng W, et al. DACHPt-loaded nanoparticles self-assembled from biodegradable dendritic copolymer polyglutamic acid-B-D-α-tocopheryl polyethylene glycol 1000 succinate for multidrug resistant lung cancer therapy. Front Pharmacol. 2018; 9:119. https://doi.org/10.3389/fphar.2018.00119 PMid:29515445 PMCid:PMC5826327

169. Zhang R, Ru Y, Gao Y, Li J, Mao S. Layer-by-layer nanoparticles co-loading gemcitabine and platinum (IV) prodrugs for synergistic combination therapy of lung cancer. Drug Des Devel Ther. 2017; 11:2631-42. https://doi.org/10.2147/DDDT.S143047 PMid:28919713 PMCid:PMC5592956

170. Nascimento AV, Singh A, Bousbaa H, Ferreira D, Sarmento B, Amiji MM. Combinatorial designed epidermal growth factor receptor-targeted chitosan nanoparticles for encapsulation and delivery of lipid-modified platinum derivatives in wild-type and resistant non-small-cell lung cancer cells. Mol Pharm. 2015; 12(12):4466-77. https://doi.org/10.1021/acs.molpharmaceut.5b00642 PMid:26523837

171. Shi C, Yu H, Sun D, Ma L, Tang Z, Xiao Q, et al. Cisplatin-loaded polymeric nanoparticles: Characterization and potential exploitation for the treatment of non-small cell lung carcinoma. Acta Biomater. 2015; 18:68-76. https://doi.org/10.1016/j.actbio.2015.02.009 PMid:25707922

172. Bao YW, Hua XW, Chen X, Wu FG. Platinum-doped carbon nanoparticles inhibit cancer cell migration under mild laser irradiation: Multi-organelle-targeted photothermal therapy. Biomater. 2018; 183:30-42. https://doi.org/10.1016/j.biomaterials.2018.08.031 PMid:30149228

173. Shi H, Xu M, Zhu J, Li Y, He Z, Zhang Y, et al. Programmed co-delivery of platinum nanodrugs and gemcitabine by a clustered nanocarrier for precision chemotherapy for NSCLC tumors. J mater Chem B. 2020; 8(2):332-42. https://doi.org/10.1039/C9TB02055A PMid:31825452

174. Yang C, Wang M, Zhou J, Chi Q. Bio-synthesis of peppermint leaf extract polyphenols capped nano-platinum and their in vitro cytotoxicity towards colon cancer cell lines (HCT116). Mater Sci Eng C Mater Biol Appl. 2017; 77:1012-6. https://doi.org/10.1016/j.msec.2017.04.020 PMid:28531972

175. Alyami NM, Almeer R, Alyami HM. Role of green synthesized platinum nanoparticles in cytotoxicity, oxidative stress, and apoptosis of human colon cancer cells (HCT-116). Heliyon. 2022; 8:e11917.https://doi.org/10.1016/j.heliyon.2022.e11917 PMid:36506358 PMCid:PMC9732314

176. Lee DY, Kim JY, Lee Y, Lee S, Miao W, Kim HS, et al. Black pigment gallstone inspired platinum-chelated bilirubin nanoparticles for combined photoacoustic imaging and photothermal therapy of cancers. Angew Chem Int Ed Engl. 2017; 56(44):13684-8. https://doi.org/10.1002/anie.201707137 PMid:28869355

177. Tsai MH, Pan CH, Peng CL, Shieh MJ. Panitumumab-conjugated Pt-drug nanomedicine for enhanced efficacy of combination targeted chemotherapy against colorectal cancer. Adv Healthc Mater. 2017; 6(13):1700111. https://doi.org/10.1002/adhm.201700111 PMid:28418176

178. Zhang Q, Kuang G, Zhou D, Qi Y, Wang M, Li X, et al. Photoactivated poly prodrug nanopartcles for effective light-controlled Pt(IV) and siRNA co-delivery to achieve synergistic cancer therapy. J Mater Chem B. 2020; 8(27):5903-11. https://doi.org/10.1039/D0TB01103G PMid:32538396

179. Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt (IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci USA. 2008; 105(45):17356-61. https://doi.org/10.1073/pnas.0809154105 PMid:18978032 PMCid:PMC2582270

180. Dhar S, Kolishetti N, Lippard SJ, Farokhzad OC. Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci USA. 2011; 108(5):1850-5. https://doi.org/10.1073/pnas.1011379108 PMid:21233423 PMCid:PMC3033286

181. Zhou Z, Fan T, Yan Y, Zhang S, Zhou Y, Deng H, et al. One stone with two birds: Phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors. Biomater. 2019; 194:130-8. https://doi.org/10.1016/j.biomaterials.2018.12.024 PMid:30593938

182. Tanaka M, Okinaga T, Iwanaga K, Matsuo K, Toyono T, Sasaguri M, et al. Anticancer effect of novel platinum nanocomposite beads on oral squamous cell carcinoma cells. J Biomed Mater Res Appl Biomater. 2019; 107(7):2281-7. https://doi.org/10.1002/jbm.b.34320 PMid:30689290

183. Mukherjee S, Kotchenlakota R, Haque S, Bhattacharya D, Kumar JM, Chakravarty S, et al. Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma. Mater Sci Eng C Mater Biol Appl. 2020; 108:110375. https://doi.org/10.1016/j.msec.2019.110375 PMid:31924026

184. Dhar S, Liu Z, Thomale J, Dai H, Lippard SJ. Targeted single-wall carbon nanotube-mediated Pt (IV) prodrug delivery using folate as a homing device. J Am Chem Soc. 2008; 130:11467-76. https://doi.org/10.1021/ja803036e PMid:18661990 PMCid:PMC2536766

185. Ruiz AL, Arribas EV, McEnnis K. Poly(lactic-co-glycolic acid) encapsulated platinum nanoparticles for cancer treatment. Mater Adv. 2022; 3:2858-70. https://doi.org/10.1039/D1MA01155C

186. Park DK, Lee SJ, Lee J, Choi MY, Han SW. Effect of polymeric stabilizers on the catalytic activity of Pt nanoparticles synthesized by laser ablation. Chem Phys Lett. 2010; 484:254-7. https://doi.org/10.1016/j.cplett.2009.11.031

187. Czubacka E, Czerczak S. Are platinum nanoparticles safe to human health? MedycynaPracy. 2019; 70(4):487-95. https://doi.org/10.13075/mp.5893.00847 PMid:31162484

188. Mandal AK, Majhi R. Cerium oxide nanoparticles as delivery system against various diseases. Ind J Appl Res. 2023; 13(10): https://doi.org/10.36106/ijar