Synthesis and characterization of a biocompatible azide-containing platform based on nanodiamonds for click chemistry functionalization

Introduction. This work presents a strategy for creating a modular nanoplatform for targeted therapy based on chemically modified nanodiamonds.

The objective was to synthesize and investigate a modified nanodiamond, ND-PEG₄-N₃, containing a reactive azide group (–N₃) for subsequent use as the basis of targeted therapy.

Methods and materials. The Steglich esterification was used for the covalent attachment of the ligand. Successful surface functionalization was confirmed by CP/MAS NMR, Fourier-transform infrared spectroscopy, and XPS. Furthermore, the cytotoxicity of both plain nanodiamonds and ND-PEG4-N3 was investigated using the HEK293 cell line.

Results. The presence of the azide group enables the subsequent selective conjugation with target ligands via the azidealkyne cycloaddition reaction. The data obtained confirm the successful chemical modification of the surface of nanodiamonds.

Conclusion. The results confirm that ND-PEG₄-N₃ is a promising and biocompatible foundation for the development of biomedical materials with the necessary functional potential to create targeted therapy systems.

1. Shenderova O. A., McGuire G. E. Science and engineering of nanodiamond particle surfaces for biological applications (Review) // Biointerphases. 2015;10(3. 030802.

2. Paci J. T., Man H. B., Saha B. et al. Understanding the surfaces of nanodiamonds // Journal of Physical Chemistry C. American Chemical Society. 2013;117(33):17256–17267.

3. Xu J., Chow E. K.-H. Biomedical applications of nanodiamonds: From drug-delivery to diagnostics // SLAS Technol. 2023.

4. Dolmatov V. Y. Detonation synthesis ultradispersed diamonds: properties and applications // Russian Chemical Reviews. 2001;70(7):607–626.

5. Holt K. B. Diamond at the nanoscale: applications of diamond nanoparticles from cellular biomarkers to quantum computing // Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. 2007;365(1861):2845–2861.

6. Chow E. K., Zhang X. Q., Chen M. et al. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment // Sci Transl Med. 2011;3(73):73ra21.

7. Neitzel I., Mochalin V., Knoke I. et al. Mechanical properties of epoxy composites with high contents of nanodiamond // Compos Sci Technol. 2011;71(5):710–716.

8. Qin J. X., Yang X. G., Lv C. F. et al. Nanodiamonds: Synthesis, properties, and applications in nanomedicine // Mater Des. 2021;210:110091.

9. Hens S. C., Cunningham G., Tyler T. et al. Nanodiamond bioconjugate probes and their collection by electrophoresis // Diam Relat Mater. 2008;17(11):1858–1866.

10. Xu D., Liu M., Zhang Q. et al. Preparation of water dispersible and biocompatible nanodiamond-poly(amino acid) composites through the ring-opening polymerization // Materials Science and Engineering: C. 2018;91:496–501.

11. Jung H. S., Neuman K. C. Surface Modification of Fluorescent Nanodiamonds for Biological Applications // Nanomaterials. 2021;11(1):153.

12. Zhao L., Xu Y. H., 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.

13. Berdichevskiy G. M., Vasina L. V., Ageev S. V. et al. A comprehensive study of biocompatibility of detonation nanodiamonds // J Mol Liq. 2021;332:115763.

14. Panich A. M. Nuclear magnetic resonance studies of nanodiamond surface modification // Diam Relat Mater. 2017;79:21–31.

15. Petit T., Puskar L. FTIR spectroscopy of nanodiamonds: Methods and interpretation // Diam Relat Mater. 2018;89:52–66.