Active targeting of nanoparticles: An innovative technology for drug delivery in cancer therapeutics
In nanomedicines, currently a wide array of reported nanoparticle systems is being explored by targeting schemes which suggests great potential of targeted delivery to revolutionize cancer therapeutics. This review gives insight into recent challenges in modification of nanoparticle systems for enhanced cancer therapy acknowledged by researchers to date and also outlines different major targeting strategies of nanoparticle systems that have been utilized for the delivery of therapeutics or imaging agents, targeting ligand and cross-linking agent to cancer which was divided into three sections: 1) Angiogenesis associated targeting, 2) Uncontrolled cell proliferation targeting and 3) Tumor cell targeting.
Keywords: nanoparticles, tumor cells, active targeting, targeting strategies, targeting ligands
2. Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, et al. NP targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer research. 2005;65(12):5317-24.
3. Lalani R, Misra A, Amrutiya J, Patel H, Bhatt P, Patil SK. Approaches and Recent Trends in Gene Delivery for Treatment of Atherosclerosis. Recent patents on drug delivery & formulation. 2016;10(2):141-55.
4. Bellocq NC, Pun SH, Jensen GS, Davis ME. Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjugate chemistry. 2003;14(6):1122-32.
5. Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic NPs. Advanced drug delivery reviews. 2010;62(11):1052-63.
6. Vhora I, Patil S, Bhatt P, Misra A. Protein- and Peptide-drug conjugates: an emerging drug delivery technology. Advances in protein chemistry and structural biology. 2015;98:1-55.
7. Betancourt T, Brown B, Brannon-Peppas L. Doxorubicin-loaded PLGA NPs by nanoprecipitation: preparation, characterization and in vitro evaluation. Nanomedicine (London, England). 2007;2(2):219-32.
8. Lowery AR, Gobin AM, Day ES, Halas NJ, West JL. Immunonanoshells for targeted photothermal ablation of tumor cells. International journal of nanomedicine. 2006;1(2):149-54.
9. Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of controlled release : official journal of the Controlled Release Society. 2010;148(2):135-46.
10. Elsabahy M, Wooley KL. Design of polymeric NPs for biomedical delivery applications. Chemical Society reviews. 2012;41(7):2545-61.
11. Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology applications in cancer. Annual review of biomedical engineering. 2007;9:257-88.
12. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang P-S, Wang S-K, et al. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield. Science. 2011;334(6059):1097.
13. Singh R, Lillard JW, Jr. NP-based targeted drug delivery. Experimental and molecular pathology. 2009;86(3):215-23.
14. Yoo D, Lee JH, Shin TH, Cheon J. Theranostic magnetic NPs. Accounts of chemical research. 2011;44(10):863-74.
15. Ulbrich K, Holá K, Šubr V, Bakandritsos A, Tuček J, Zbořil R. Targeted Drug Delivery with Polymers and Magnetic NPs: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies. Chemical Reviews. 2016;116(9):5338-431.
16. Fernandez-Fernandez A, Manchanda R, McGoron AJ. Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Applied biochemistry and biotechnology. 2011;165(7-8):1628-51.
17. Mohamed F, van der Walle CF. Engineering Biodegradable Polyester Particles With Specific Drug Targeting and Drug Release Properties. Journal of Pharmaceutical Sciences. 2008;97(1):71-87.
18. Lee DE, Koo H, Sun IC, Ryu JH, Kim K, Kwon IC. Multifunctional NPs for multimodal imaging and theragnosis. Chemical Society reviews. 2012;41(7):2656-72.
19. Tandel H, Bhatt P, Jain K, Shahiwala A, Misra A. In-Vitro and In-Vivo Tools in Emerging Drug Delivery Scenario: Challenges and Updates. 2018. p. 19-42.
20. Patil S, Bhatt P, Lalani R, Amrutiya J, Vhora I, Kolte A, et al. Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency. RSC Advances. 2016;6(112):110951-63.
21. Bhatt P, Lalani R, Vhora I, Patil S, Amrutiya J, Misra A, et al. Liposomes encapsulating native and cyclodextrin enclosed paclitaxel: Enhanced loading efficiency and its pharmacokinetic evaluation. International Journal of Pharmaceutics. 2018;536(1):95-107.
22. Patil S, Lalani R, Bhatt P, Vhora I, Patel V, Patel H, et al. Hydroxyethyl substituted linear polyethylenimine for safe and efficient delivery of siRNA therapeutics. RSC Advances. 2018;8(62):35461-73.
23. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the ENHANCED PERMEABILITY AND RETENTION (EPR) effect in macromolecular therapeutics: a review. Journal of controlled release : official journal of the Controlled Release Society. 2000;65(1-2):271-84.
24. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249-57.
25. Danquah MK, Zhang XA, Mahato RI. Extravasation of polymeric nanomedicines across tumor vasculature. Advanced drug delivery reviews. 2011;63(8):623-39.
26. Bazak R, Houri M, Achy SE, Hussein W, Refaat T. Passive targeting of NPs to cancer: A comprehensive review of the literature. Molecular and clinical oncology. 2014;2(6):904-8.
27. Chipman SD, Oldham FB, Pezzoni G, Singer JW. Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. International journal of nanomedicine. 2006;1(4):375-83.
28. Bae YH, Park K. Targeted drug delivery to tumors: myths, reality and possibility. Journal of controlled release : official journal of the Controlled Release Society. 2011;153(3):198-205.
29. Siegler EL, Kim YJ, Wang P. Nanomedicine targeting the tumor microenvironment: Therapeutic strategies to inhibit angiogenesis, remodel matrix, and modulate immune responses. Journal of Cellular Immunotherapy. 2016;2(2):69-78.
30. Vieira DB, Gamarra LF. Advances in the use of nanocarriers for cancer diagnosis and treatment. Einstein (Sao Paulo, Brazil). 2016;14(1):99-103.
31. Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H. Nanomedicine--challenge and perspectives. Angewandte Chemie (International ed in English). 2009;48(5):872-97.
32. Davis ME, Chen ZG, Shin DM. NP therapeutics: an emerging treatment modality for cancer. Nature reviews Drug discovery. 2008;7(9):771-82.
33. Petros RA, DeSimone JM. Strategies in the design of NPs for therapeutic applications. Nature reviews Drug discovery. 2010;9(8):615-27.
34. Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P. Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chemical Society reviews. 2013;42(3):1147-235.
35. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for NP systems in cancer therapeutics. Advanced drug delivery reviews. 2008;60(15):1615-26.
36. Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC. Targeted polymeric therapeutic NPs: design, development and clinical translation. Chemical Society reviews. 2012;41(7):2971-3010.
37. Lammers T, Kiessling F, Hennink WE, Storm G. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. Journal of controlled release : official journal of the Controlled Release Society. 2012;161(2):175-87.
38. Shi J, Xiao Z, Kamaly N, Farokhzad OC. Self-assembled targeted NPs: evolution of technologies and bench to bedside translation. Accounts of chemical research. 2011;44(10):1123-34.
39. Vhora I, Patil S, Bhatt P, Gandhi R, Baradia D, Misra A. Receptor-targeted drug delivery: current perspective and challenges. Therapeutic delivery. 2014;5(9):1007-24.
40. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nature reviews Cancer. 2002;2(10):750-63.
41. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer research. 1993;53(19):4727-35.
42. Lalani RA, Bhatt P, Rathi M, Misra A. Abstract 2063: Improved sensitivity and in vitro efficacy of RGD grafted PEGylated gemcitabine liposomes in RRM1 siRNA pretreated cancer cells. Cancer research. 2016;76(14 Supplement):2063-.
43. Li L, Wartchow CA, Danthi SN, Shen Z, Dechene N, Pease J, et al. A novel antiangiogenesis therapy using an integrin antagonist or anti-Flk-1 antibody coated 90Y-labeled NPs. International journal of radiation oncology, biology, physics. 2004;58(4):1215-27.
44. Hood JD, Bednarski M, Frausto R, Guccione S, Reisfeld RA, Xiang R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science. 2002;296(5577):2404-7.
45. Ruoslahti E. Fibronectin and its integrin receptors in cancer. Advances in cancer research. 1999;76:1-20.
46. Bhatt P, Lalani R, Mashru R, Misra A. Abstract 2065: Anti-FSHR antibody Fab’ fragment conjugated immunoliposomes loaded with cyclodextrin-paclitaxel complex for improved in vitro efficacy on ovarian cancer cells. Cancer research. 2016;76(14 Supplement):2065-.
47. Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989;59(6):1203-11.
48. Dienst A, Grunow A, Unruh M, Rabausch B, Nor JE, Fries JW, et al. Specific occlusion of murine and human tumor vasculature by VCAM-1-targeted recombinant fusion proteins. Journal of the National Cancer Institute. 2005;97(10):733-47.
49. Genis L, Galvez BG, Gonzalo P, Arroyo AG. MT1-MMP: universal or particular player in angiogenesis? Cancer metastasis reviews. 2006;25(1):77-86.
50. Sato H, Takino T, Miyamori H. Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer science. 2005;96(4):212-7.
51. Deryugina EI, Bourdon MA, Jungwirth K, Smith JW, Strongin AY. Functional activation of integrin alpha V beta 3 in tumor cells expressing membrane-type 1 matrix metalloproteinase. International journal of cancer. 2000;86(1):15-23.
52. Scallon BJ, Snyder LA, Mark Anderson G, Chen Q, Yan L, Weiner LM, et al. A Review of Antibody Therapeutics and Antibody-Related Technologies for Oncology. Journal of Immunotherapy. 2006;29(4):351-64.
53. Bhatt P, Vhora I, Patil S, Amrutiya J, Bhattacharya C, Misra A, et al. Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status. Journal of controlled release : official journal of the Controlled Release Society. 2016;226:148-67.
54. Laskin JJ, Sandler AB. Epidermal growth factor receptor: a promising target in solid tumours. Cancer treatment reviews. 2004;30(1):1-17.
55. Patel J, Amrutiya J, Bhatt P, Javia A, Jain M, Misra A. Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA NPs into EGFR overexpressed lung tumour cells. Journal of microencapsulation. 2018;35(2):204-17.
56. Pan X, Wu G, Yang W, Barth RF, Tjarks W, Lee RJ. Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor for targeting of EGFR. Bioconjugate chemistry. 2007;18(1):101-8.
57. Rainov NG, Soling A. Technology evaluation: TransMID, KS Biomedix/Nycomed/Sosei/PharmaEngine. Current opinion in molecular therapeutics. 2005;7(5):483-92.
58. Gandhi M, Bhatt P, Chauhan G, Gupta S, Misra A, Mashru R. IGF-II-Conjugated Nanocarrier for Brain-Targeted Delivery of p11 Gene for Denhanced permeability and retention (EPR)ession. AAPS PharmSciTech. 2019;20(2):50.
59. Faulk WP, Taylor CG, Yeh CJ, McIntyre JA. Preliminary clinical study of transferrin-adriamycin conjugate for drug delivery to acute leukemia patients. Mol Biother. 1990;2(1):57-60.
60. Low PS, Antony AC. Folate receptor-targeted drugs for cancer and inflammatory diseases. Advanced drug delivery reviews. 2004;56(8):1055-8.
61. Shmeeda H, Mak L, Tzemach D, Astrahan P, Tarshish M, Gabizon A. Intracellular uptake and intracavitary targeting of folate-conjugated liposomes in a mouse lymphoma model with up-regulated folate receptors. Molecular cancer therapeutics. 2006;5(4):818-24.
62. Tan WB, Jiang S, Zhang Y. Quantum-dot based NPs for targeted silencing of HER2/neu gene via RNA interference. Biomaterials. 2007;28(8):1565-71.
63. Yewale C, Baradia D, Patil S, Bhatt P, Amrutiya J, Gandhi R, et al. Docetaxel loaded immunoNPs delivery in EGFR overexpressed breast carcinoma cells. Journal of Drug Delivery Science and Technology. 2018;45:334-45.
64. Tseng CL, Wang TW, Dong GC, Yueh-Hsiu Wu S, Young TH, Shieh MJ, et al. Development of gelatin NPs with biotinylated EGF conjugation for lung cancer targeting. Biomaterials. 2007;28(27):3996-4005.
65. Zhang Y, Zhang J. Surface modification of monodisperse magnetite NPs for improved intracellular uptake to breast cancer cells. Journal of colloid and interface science. 2005;283(2):352-7.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).