Immobilization of doxorubicin on the olygoelectrolytic polymeric carrier VEP-GMA-PEG increases its and anticancer activity cellular uptake
| Autor: | Yu. V. Senkiv, A. R. Ryabtseva, P. Heffeter, N. M. Boiko, E. A. Shlyakhtina, N. E. Mitina, W. Berger, O. S. Zaichenko, R. S. Stoika |
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| Jazyk: | English<br />Ukrainian |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Біологічні студії, Vol 6, Iss 2, Pp 5-16 (2012) |
| Druh dokumentu: | article |
| ISSN: | 1996-4536 2311-0783 |
| DOI: | 10.30970/sbi.0602.225 |
| Popis: | Application of special systems for drug delivery into target cells might be useful for overcoming several problems in treatment of dangerous diseases. These are: consequences of nonspecific negative effects of drugs towards healthy cells, low sensitivity of cancer cells to anticancer drugs used in doses that are non-toxic for the organism, resistance of tumor cells to anticancer drugs and of the pathogenic microorganisms to the antibiotics. Here we studied the efficiency of application of novel nanoscale drug delivery system in tumor cell lines, including drug-resistant ones. The polyethylene glycol (PEG)-modified polymeric carrier VEP-GMA used in this study, was synthesized at the Department of Organic Chemistry of Lviv National Polytechnic University. We compared the effect of free doxorubicin and of this anticancer drug immobilized on the polymeric carrier, towards human tumor cells. It was found that such immobilization of doxorubicin significantly enhanced the cytotoxic action of this drug towards human lung carcinoma A549 cells, human colorectal carcinoma HCT116 cells, human breast carcinoma MCF-7 cells and their doxorubicin-resistant MCF-7/ADR subline. The results of our studies demonstrated that using doxorubicin complex with novel polymeric nanoscale carrier VEP-GMA-PEG permitted reducing the active dose of doxorubicin in cancer cells at least 10 times, comparing with such dose of this anticancer drug used in free form. Since the antineoplastic effect of carrier-immobilized doxorubicin was maintained, these results suggest a potential reduction of negative side effects of the corresponding chemotherapy. It was shown that the uptake by tumor cells of the carrier- immobilized doxorubicin was significantly enhanced comparing with such uptake of free doxorubicin. Our data demonstrated that neither macropinocytosis, nor endocytosis can be responsible for the uptake of doxorubicin that is immobilized on the nanosized polymeric carrier. Our future experiments are focused on the improvement of characteristics of this carrier by means of its specific functionalization aimed at reaching its addressed action towards tumor cells in vitro and in vivo. |
| Databáze: | Directory of Open Access Journals |
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