Synthesis and Characterization of Nanodiamond-Doxorubicin (Dox) Conjugate for Effective Delivery against MCF-7 Cell Lines
In this work, we have introduced a carbon nanomaterial (nanodiamond), to bind with anticancer drug doxorubicin (DOX) with via amide bond conjugation for cancer drug delivery and therapy. Nanodiamond (ND) was initially carboxylated by the surface modification along the treatment with strong alkaline solution (H2SO4:HNO3) and then activated the carboxyl moiety of ND with the addition of EDC. Anticancer drugs were bound to the ND through a succession of chemical modifications by adipic acid dihydrazide (ADH). The ND-Drug conjugate was analyzed by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy, Fourier Transform Infrared (FTIR) Spectroscopy and Mass Spectroscopy (MS), Atomic Force Microscopy (AFM), Particle size, Zeta potential, Drug release, SRB assay against MCF-7 cells, and DNA fragmentation. Spectroscopic analysis confirms the conjugation of nanodiamond with different anticancer drug. AFM photomicrograph represents the surface morphological features of ND-DOX conjugates. In- vitro investigation showed that ND-DOX conjugates have slow and sustained drug release characteristics. In-vitro cytotoxicity studies, an enormous cytotoxic potential of ND-Drug conjugates were showed against cancer cell line. Above all findings were suggested that the ND-DOX conjugates may be a potential inhibitor of MCF-7 cancer cells to act as a drug candidate. According to all these data it can be confirm that the ND-DOX conjugates could be an effective agent for drug delivery and could be promising in future for tumor targeting strategy.
Keywords: Nanodiamond, Sustained Release, Drug Delivery, Cytotoxicity, Conjugates
2. Saenz del Burgo L, Pedraz J, Orive G. Advanced nano vehicles for cancer management. Drug Discovery Today 2014; 19(10): 1659-1670.
3. Barreto JA, O’Malley W, Kubeil, M et al., Cancer research: nanomaterials: applications in cancer imaging and therapy (Adv. Mater. 12/2011). Advanced Materials 2011; 23(12): 18-40.
4. Gong H, Cheng L, Xiang J et al., Near-Infrared absorbing polymeric nanoparticles as a versatile drug carrier for cancer combination therapy. Advanced Functional Materials 2013; 23(48): 6059-6067.
5. Greiner NR, Phillips DS, Johnson JD et al., Diamonds in detonation soot. Nature 1988; 333(6172): 440-442.
6. Vereschagin A, Sakovich G, Komarov V et al., Properties of ultrafine diamond clusters from detonation synthesis. Diamond and Related Materials 1994; 3(1-2): 160-162.
7. Kuznetsov VL, Chuvilin AL, Butenko YV et al., Onion-like carbon from ultra-disperse diamond. Chemical Physics Letters 1994; 222(4): 343-348.
8. Liu Y, Gu Z, Margrave JL et al., Functionalization of nanoscale diamond powder: fluoro-, alkyl-, amino-, and amino acid-nanodiamond derivatives. Chemistry of Materials 2004; 16(20): 3924-3930.
9. Zhang X, Chen M, Lam R, Xu X et al., Polymer-Functionalized nanodiamond platforms as vehicles for gene delivery. ACS Nano 2009; 3(9): 2609-2616.
10. Bhadra D, Yadav A, Bhadra S et al., Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting. International Journal of Pharmaceutics 2005; 295(1-2): 221-233.
11. Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nature Protocols 2006; 1(3): 1112-1116.
12. Yawata A, Adachi M, Okuda H et al., Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells. Oncogene 1998; 16(20): 2681-2686.
13. Bampton ET, Goemans CG, Niranjan D et al., The Dynamics of Autophagy Visualised in Live Cells: from Autophagosome Formation to Fusion with Endo/lysosomes. Autophagy 2005; 1(1): 23-36.
14. Kabeya Y. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO Journal 2000; 19(21): 5720-5728.
15. Klionsky DJ. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 2008; 4: 151-175.
16. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems - a review (part 2). Tropical Journal of Pharmaceutical Research 2013; 12(2): 265-273.
17. Zhu H, Wang Y, Hussain A et al., Nanodiamond mediated co-delivery of doxorubicin and malaridine to maximize synergistic anti-tumor effects on multi-drug resistant MCF-7/ADR cells. Journal of Materials Chemistry B 2017; 5(19): 3531-3540.
18. Hu X, Liu S, Huang Y et al., Biodegradable block copolymer-doxorubicin conjugates via different linkages: preparation, characterization, and in vitro evaluation. Biomacromolecules 2010; 11(8): 2094-2102.
19. Ansari SA, Satar R et al., Role of nanodiamonds in drug delivery and stem cell therapy. Iranian Journal of Biotechnology 2016; 14(3): 130-141.
20. Xu P, Van Kirk E, Zhan Y et al., Targeted charge-reversal nanoparticles for nuclear drug delivery. Angewandte Chemie International Edition 2007; 46(26): 4999-5002.
21. Sun C, Liu Y, Du J et al., Facile generation of tumor-ph-labile linkage-bridged block copolymers for chemotherapeutic delivery. Angewandte Chemie 2015; 128(3): 1022-1026.
22. Zhao L, Xu Y, Akasaka T et al., Polyglycerol-coated nanodiamond as a macrophage-evading platform for selective drug delivery in cancer cells. Biomaterials 2014; 35(20): 5393-5406.
23. Wu L, Zou Y, Deng C et al., Intracellular release of doxorubicin from core-crosslinked polypeptide micelles triggered by both pH and reduction conditions. Biomaterials 2013; 34(21): 5262-5272.
24. Wąsowicz M, Ficek M, Wróbel M et al., Haemocompatibility of modified nanodiamonds. Materials 2017; 10(4): 352.
25. Zhang W, Shi Y, Chen Y et al., Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance. European Journal of Pharmaceutics and Biopharmaceutics 2010; 75(3): 341-353.
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