ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
"Biotechnologia Acta" v. 6, no. 3, 2013
https://doi.org/10.15407/biotech6.03.053
Р. 53-62, Bibliography 12, Ukrainian.
Universal Decimal classification: 54.057+547.311+576.5+577+615.9+616-006
1Institute of Cell Biology of National Academy of Sciences of Ukraine, Lviv
2National University «Lviv Polytechnics», Ukraine
3Lviv National Ivan Franko University, Faculty of Biology, Ukraine
The main tasks of modern biopharmaceutics are focused at the development of new nanoscale carriers with low toxicity, given size, regulated response to local and remote effects, and capability of visualization of drug action and diagnostic results. A novel oligomeric carrier VAMANG-MP for delivery of the anticancer drug doxorubicin to tumor cells of different lines have been used. The synthesized oligomeric carrier was additionally functionalized by phosphatitylcholine. It was demonstrated that such delivery of doxorubicin to the target cells permits 10 times decreasing of its acting cytotoxic dose comparing with such dose of free doxorubicin, with preserving similar level of the antineoplastic effect. This dose-specific effect was demonstrated both in vitro towards various mammalian tumor cells, and in vivo towards mice with experimental NK/Ly lymphoma was shown. Action of immobilized doxorubicin was followed by more intense formation of vesicles on a surface of the target cells in vitro, and by their inter-nucleosomal DNA fragmentation as compared to action of free doxorubicin, as well as by appearance of a higher amount of the dead cells in the ascytic fluid of the treated NK/Ly lymphoma mice. Thus, the synthesized nanoscale olygoelectrolytic carrier is a perspective system for delivery of anticancer drugs to target cells.
Key words: doxorubicin delivery, tumor cells, olygo electrolytes, nanoscale particles.
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2013
References
1. Caruthers S. D., Wickline S. A., Lanza G. M., Nanotechnological applications in medicine. Curr. Opin. Biotechnol. 2007, V. 18, P. 26–30.
https://doi.org/10.1016/j.copbio.2007.01.006
2. Clavinas H., Crajcsi P., Cserepes J., Sarcadi B. The role of ABC transporters in drug resistance, metabolism and toxicity. Curr. Drug Deliv. 2004, V. 1, P. 27–42.
https://doi.org/10.2174/1567201043480036
3. J?ger E., J?ger A., Chytil P. Combination chemotherapy using core-shell nanoparticles through the self-assembly of HPMA-based copolymers and degradable polyester. J. Contr. Rel. 2012, 3659(12), 00805-X.
4. Wang T., Deepa B., Fagbohun O. A. Enhanced binding and killing of target tumor cells by drug-loaded liposomes modified with tumor-specific phage fusion coat protein. Nanomedicine (Lond) . 2010, 5(4),?563–574.
5. Zhang F., Zhu L., Liu G. Imaging of Tumor Response to Doxil. Theranostics. 2011,V. 1, P. 302–309.
https://doi.org/10.7150/thno/v01p0302
6. Euliss L. E., DuPont J. A., Gratton S., DeSimone J. Imparting size, shape, and composition control of materials for nanomedicine. Chem. Soc. Rev. 2006, 35(11), 1095–2004.
https://doi.org/10.1039/b600913c
7. Sopin Ye. F., Vynogradova R. P. Fundamentals of biochemical methods. K.: Vyshcha shkola. 1975, 244 p. (In Ukrainian).
8. Lu Ch., Zhu F., Cho Y.-Y. Cell Apoptosis: Requirement of H2AX in DNA Ladder Formation but not for the Activation of Caspase-3. Mol. Cell. 2006, 23(1),?121–132.
https://doi.org/10.1016/j.molcel.2006.05.023
9. Singh N. D., Sharma A. K. , P. Patil Studies on Apoptotic Changes in Combined Toxicity of Citrinin and Endosulfan in Pregnant Wistar Rats and Their Fetuses. Toxicol. Int. 2012, 19(2),?138–143.
10. Savic R., Luo L. B., Eisenberg A., Maysinger D. Nanocontainers distribute to defined cytoplasmic organelles. Science. 2003, V.?300, Р. 615–618.
11. Landowski T., Gleason-Gurman M., Dalton W. Blood. 1997, V. 6, P. 1854–1861.
12. Kahizuka A., Miller W., Umesono K. Cell. 1991, V. 66, P. 663–667.
https://doi.org/10.1016/0092-8674(91)90112-C