Anti-cancer active nano carbon drug conjugate based on an Aryl Azide using the classical ‘click’ chemistry

Articles in Press

Document Type : Research Paper

Authors

1 TERI School of Advanced Studies, (Plot No. 10, Vasant Kunj Institutional Area), New Delhi-110070, India

2 BEMMS, 4C-1G, Foundation for Innovation and Technology Transfer, Indian Institute of Delhi, Hauz Khas, New Delhi, Delhi 110016, India

3 Regional Centre for Biotechnology (RCB), Under the Auspices of UNESCO-DBT, (NCR Biotech Science Cluster), 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India

4 Manav Rachna International Institute of Research and Studies, Faridabad, India

5 Ex: Head (Chemistry Department) and Dean (Academics), St Stephen's College, Delhi, 110007; Amity University, Noida, Uttar Pradesh-201313, India; Adjunct Prof. (Hony.), Deakin University, Australia; Teri Deakin Nano Biotechnology Research Centre, Gwal Pahari, TERI Gram, The Energy and Resources Institute, Gurgaon Faridabad Road, Gurgaon, Haryana 122 002, India

Abstract

Objective(s): Nano Carbon Drug Conjugates (NCDCs) are created by attaching therapeutic agents to nanocarbon structures such as Fullerene (C60), Single-Walled Carbon Nanotubes (SWCNT), Graphene Oxide (GO), and Reduced Graphene Oxide (rGO). These conjugated nanocarriers exhibit outstanding characteristics, including a high surface area, ease of functionalization, and the ability to penetrate biological barriers.
Materials and Methods: The conjugation of drugs to these nanocarriers enhances the solubility, stability, and bioavailability of the drugs, potentially overcoming the limitations of conventional drug delivery systems, such as cytotoxicity and side effects. The design of Nano Carbon Drug Conjugates (NCDCs) requires careful consideration of factors like the Drug-to-Nanocarbon Ratio (DNR), the choice of linker, and the selection of a targeting moiety to ensure selective accumulation in diseased tissues while minimizing off-target effects. NCDCs have broad applications in various medical fields, with a significant emphasis on cancer therapy  (oncology), where they can deliver cytotoxic agents directly to tumor cells, thereby reducing systemic toxicity.
Results: This paper focuses on synthesis and characterizing a novel nanocarbon drug conjugate based on conventional 'click' chemistry, offering an improved approach for conjugating nanocarbons [(e.g. Fullerene C60)] with therapeutic agents. Additionally, it explores whether these conjugates could serve as theranostic agents.
Conclusions: The cytotoxicity of the newly prepared conjugate was evaluated using the MTT assay, and the cell survival rate was 87.68% at 10 µM and 79.73% at 20 µM, respectively, after 36 hours of treatment. Western blot analysis revealed significant expression of apoptosis markers, including Bax, Caspase 9, Cleaved Caspase 9, and Cytc, at 10 µM and 20 µM concentrations.

Keywords

References

  1. Sheingold BH, Hahn JA. The history of healthcare quality: the first 100 years 1860–1960. Intern J Appl Nonlinear Sci. 2014; 1:18–22.
  2. Liebler D, Guengerich F. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov. 2005; 4: 410–420.
  3. Dubey D, Dhiman S, Koner AL. Review of Carbon Dot-Based Drug Conjugates for Cancer Therapy. ACS Applied Nano Materials. 2023; 6 (6): 4078-4096.
  4. De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008; 3(2): 133-149.
  5. Tiwari G, Tiwari R, Srivastava B, Bhati L, Pandey S, Pandey P, Bannerjee SK. Drug Delivery Systems: An Updated Review. Intern J Pharmaceutical Investi. 2012; 2: 1-10.
  6. Emerich DF, Thanos CT. Targeted nanoparticle-based drug delivery and diagnosis.J Drug Target. 2007; 15 (3):163-183.
  7. Lu L, Duong VT, O Shalash AO, Skwarczynski M, Toth I. Chemical Conjugation Strategies for the Development of Protein-Based Subunit Nanovaccines. Vaccines. 2021; 9 (563):1-24.
  8. Yi G, Son J, Yoo J, Park C, Koo H. Application of click chemistry in nanoparticle modification and its targeted delivery. Biomater Res. 2018; 22(13): 1-8.
  9. Xie J, Lee S, Chen X. Nanoparticle-based theranostic agents. Adv Drug Deliv Rev. 2010; 62:1064–1079.
  10. Lee DE, Koo H, Sun IC, Ryu JH, Kim K, Kwon IC. Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem Soc Rev. 2012; 41: 2656–2672.
  11. Bhattacharyya D, Singh S. Nanotechnology, big things from a tiny world: a review. Int. J. u- and e-Serv, Sci. Technol. 2009; 2(3): 29–38.
  12. Emerich DF, Thanos C. The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis. Biomol Eng. 2006; 23:171–184.
  13. Singh R, Lillard Jr JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009; 86: 215–223.
  14. Biswas AK, Islam MR, Choudhary ZS, Mostafa A, Kadir MF. Nanotechnology based approaches in cancer therapeutics. Adv. Nat. Sci. Nanosci. Nanotechnol. 2014; 5(043001): 1-12.
  15. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008; 60: 1615–26.
  16. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev. 2011; 63: 131–5.
  17. Odiba A, Ukegbu C, Anunobi O, Chukwunonyelum E, Esemonu J. Making drugs safer: improving dug delivery and redicing the side effect of drug on the human biochemical system. Nanotech Rev. 2016; 5(2): 183-194.
  18. Bertozzi CR. A decade of bioorthogonal chemistry. Acc Chem Res. 2011; 44:651–53.
  19. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed. 2001; 40: 2004–2021.
  20. Yoon HY, Koo H, Kim K, Kwon IC. Molecular imaging based on metabolic glycoengineering and bioorthogonal click chemistry. Biomaterials. 2017;132: 28–36.
  21. Jewett JC, Bertozzi CR. Cu-free click cycloaddition reactions in chemical biology. Chem Soc Rev. 2010; 39: 1272–1279.
  22. Devaraj NK, Weissleder R. Biomedical applications of tetrazine cycloadditions. Acc Chem Res. 2011; 44: 816–827.
  23. Majumder N. Click chemistry in nano drug delivery system and its applications in biology. IJRPC. 2015; 5: 95–105.
  24. Colombo M, Sommaruga S, Mazzucchelli S, Polito L, Verderio P, Galeffi P, Corsi F, Tortora P, Prosperi D. Site-specific conjugation of ScFvs antibodies to nanoparticles by bioorthogonal strain-promoted alkyne–Nitrone cycloaddition. Angew Chem Int Ed. 2012; 51: 496–499.
  25. Liu R, Zhao J, Han G, Zhao T, Zhang R, Liu B, Liu Z, Zhang C, Yang L, Zhang Z. Click-functionalized SERS Nanoprobes with improved labeling efficiency and capability for cancer cell imaging. ACS Appl Mater Interfaces. 2017; 9: 38222–38229.
  26. Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front Mol Biosci. 2020; 7(193): 1-14.
  27. Wang X, Hui R, Chen Y, Wang W, Chen Y, Gong X, Jin J. Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells. Front. Pharmacol. 2019; 1434: 1-11.
  28. Chu H, Unnikrishnan B, Anand A, Mao J, Huang C. Nanoparticle-based laser desorption/ionization mass spectrometric analysis of drugs and metabolites, Journal of Food and Drug Analysis. 2018; 26(4): 1215-1228.
  29. Bandak S, Ramu A, Barenholz Y, Gabizon A. Reduced UV-induced degradation of doxorubicin encapsulated in polyethyleneglycol-coated liposomes. Pharm Res. 1999; 16(6): 841-846.
  30. Victor SP, Paul W, Jayabalana M, Sharma CP. Supramolecular hydroxyapatite complexes as theranostic near-infrared luminescent drug carriers. Cryst Eng Comm, 2014; 16: 9033–9042.
  31. Juan A, Cimas FJ, Bravo I, Pandiella A, Alberto Ocaña A, Alonso-Moreno C. An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy. Pharmaceutics. 2020; 12(802): 1-20.
  32. Bawa R. FDA and Nanotech: Baby Steps Lead to Regulatory Uncertainty. In Bio-Nanotechnology, Blackwell Publishing Ltd.: Oxford, UK, 2013, 720–732.
  33. Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?. Bioconjugate Chem.2016; 27: 2225–2238.
  34. Ghassami E, Varshosaz J, Somayeh Taymouri S. Redox Sensitive Polysaccharide Based Nanoparticles for Improved Cancer Treatment: A Comprehensive Review. Current Pharmaceutical Design. 2018; 24: 3303-3319.
  35. Behera SK, Mohanty ME, Mohapatra MA. Fluorescence Study of the Interaction of Anticancer Drug Molecule Doxorubicin Hydrochloride in Pluronic P123 and F127 Micelles. J Fluorescence. 2021; 31: 17–27.
  36. Ye L, Kollie L, Liu X, Guo W, Ying Y, Zhu J, Yang S, Yu M. Antitumor Activity and Potential Mechanism of Novel Fullerene Derivative Nanoparticles. Molecules. 2021; 26(11): 3252.
  37. Tang L, Li J, Pan T, Yin Y, Mei Y, Xiao Q, Wang R, Yan Z, Wang W. Versatile carbon nanoplatforms for cancer treatment and diagnosis: strategies, applications and future perspectives. Theranostics. 2022; 12(5): 2290-2321.

 

Nanomedicine Journal

Articles in Press, Accepted Manuscript
Available Online from 07 July 2025

Files

Share

How to cite

Statistics