The study of new anticancer drug delivery system based on the boron nitride nanoparticles

The main problem in the treatment of many cancers is multidrug resistance due to tumor progression. Using nanosized drug delivery systems allows to overcome the mechanisms of multidrug resistance of cancer, in this case, chemotherapeutic agents can effectively introduce into cancer cells by endocytosis and accumulate near the nucleus and far from ATP-binding cassette transporters. Creation of boron nitridebased drug delivery nanocarriers with high chemical and oxidative stability is one of the perspective ways. Using chemical vapor deposition spherical boron nitride particles,100–150 nm in diameter (BNNPs), with peculiar petal-like surfaces or smooth surfaces were fabricated. BNNPs were loaded with doxorubicin. Drug loading efficacy of BNNPs-DOX was about 0.095 mg/mg of particles. BNNPs-DOX were relatively stable at neutral pH, whereas DOX is effectively released from the BNNPs at acidic pH (pH 4.5–5.5). Using confocal microscopy, the uptake of BNNPs-DOX by IAR-6-1, KB-3-1, К562 cells and multidrug resistant КВ-8-5 и IS-9 cells was studied. Most of BNNPs-DOX had been co-localized with LysoTracker, indicating that BNNPs-DOX are located in the endosomes/lysosomes after intracellular delivery.

1. Kirtane A. R., Kalscheuer S. M., Panyama J. Exploiting nanotechnology to overcome tumor drug resistance: Challenges and opportunities. Adv Drug Deliv Rev 2013;65(13–14): 1731–47.

2. Amin M. L. P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights 2013;7:27–34.

3. Hillaireau H., Couvreur P. Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 2009;66(17):2873–96.

4. Couvreur P. Nanoparticles in drug delivery: past, present and future. Adv Drug Deliv Rev 2013;65(1):21–3.

5. Torchilin V. P., Lukyanov A. N. Peptide and protein drug delivery to and into tumors: challenges and solutions. Drug Discov Today 2003;8(6):259–66.

6. Oerlemans C., Bult W., Bos M. et al. Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 2010;27(12):2569–89.

7. Kaasgaard T., Andresen T. L. Liposomal cancer therapy: exploiting tumor characteristics. expert opin drug deliv 2010;7(2):225–43.

8. Mintzer M. A., Grinstaff M. W. Biomedical applications of dendrimers: a tutorial. Chem Soc Rev 2011;40(1):173–90.

9. Dreaden E. C., Mackey M. A., Huang X. et al. Beating cancer in multiple ways using nanogold. Chem Soc Rev 2011;40(7): 3391–404.

10. Lal S., Clare S. E., Halas N. J. Nanoshellenabled photothermal cancer therapy: impending clinical impact. Acc Chem Res 2008;41(12):1842–51.

11. Jokerst J. V., Gambhir S. S. Molecular imaging with theranostic nanoparticles. Acc Chem Res 2011;44(10):1050–60.

12. Trewyn B. G., Slowing I. I., Giri S. et al. Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol-gel process and applications in controlled release. Acc Chem Res 2007;40(9):846–53.

13. Bonacchi S., Genovese D., Juris R. et al. Luminescent silica nanoparticles. extending the frontiers of brightness. Angew Chem Int Ed Engl 2011;50(18):4056–66.

14. Xie J., Huang J., Li X. et al. Iron oxide nanoparticle platform for biomedical applications. Curr Med Chem 2009;16(10):1278–94.

15. Torchilin V. P. Multifunctional, stimulisensi tive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 2014;13(11):813–27.

16. Hurst J. Chapter 9 – Boron nitride nanotubes, silicon carbide nanotubes, and carbon nanotubes – a comparison of properties and applications. In: Nanotube Superfiber Materials. Elsevier, 2014. Pp. 267–287.

17. Ciofani G., Del Turco S., Genchi G. G. et al. Transferrin-conjugated boron nitride nanotubes: Protein grafting, characterization, and interaction with human endothelial cells. Int J Pharm 2012;436(1–2):444–53.

18. Ferreira T. H., Marino A., Rocca A. et al. Folate-grafted boron nitride nanotubes: possible exploitation in cancer therapy. Int J Pharm 2015;481(1–2): 56–63.

19. Li X., Wen G., Zhang T. et al. Synthesis of continuous boron nitride nanofibers by electrospinning. Physics Procedia 2012;25:185–8.

20. Lin L. X., Zheng Y., Li Z.-H. et al. A simple method to synthesize polyhedral hexagonal boron nitride nanofibers. Solid State Sci 2007;9:1099–104.

21. Lacerda L., Raffa V., Prato M. et al. Cellpenetrating CNTs for delivery of therapeutics. Nano Today 2007;2:38–43.

22. Yamakov V., Park C., Kang J. H. et al. Piezoelectric molecular dynamics model for boron nitride nanotubes. Computat Mater Sci 2014;95:362–70.

23. Ciofani G., Danti S., Genchi G. G. et al. Boron nitride nanotubes: biocompatibility and potential spill-over in nanomedicine. Small 2013;9(9–10):1672–85.

24. Salvetti A., Rossi L., Iacopetti P. et al. In vivo biocompatibility of boron nitride nanotubes: effects on stem cell biology and tissue regeneration in planarians. Nanomedicine 2015;10(12):1911–22.

25. Sukhorukova I. V., Zhitnyak I. Y., Kovalskii A. M. et al. Boron nitride nanoparticles with petal-like surface as anticancer drug delivery system. ACS Appl Mater Interfaces 2015;7(31):17217–25.

26. Tang C., Bando Y., Sato T., Kurashima K. A novel precursor for synthesis of pure boron nitride nanotubes. Chem Commun 2002;12:1290–1.

27. Bannikov G. A., Guelstein V. I., Montesano R. et al. Cell shape and organization of cytoskeleton and surface fibronectin in non-tumorigenic rat liver cultures. J Cell Sci 1982;54:47–67.

28. Park S. W., Lomri N., Simeoni L. A. et al. Analysis of P-glycoprotein-mediated membrane transport in human peripheral blood lymphocytes using the uic2 shift assay. Cytometry A 2003;53(2):67–78.

29. Richert N., Akiyama S., Shen D. et al. Multiply drug-resistant human KB carcinoma cells have decreased amounts of a 75-kDa and a 72-kDa glycoprotein. Proc Natl Acad Sci USA 1985;82(8): 2330–3.

30. Dreher M. R., Liu W., Michelich C. R. et al. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst 2006;98:335–44.

31. Champion J. A., Katare Y. K., Mitragotri S. Particle shape: A new design parameter for micro- and nanoscale drug delivery carriers. J Control Release 2007;121(1–2):3–9.