Yu. V. Senkiv1,2,4, P. Heffeter2, A. O. Riabtseva3, N. M. Boiko1, O. S. Zaichenko3, N. Ye. Mitina3, W. Berger2, R. S. Stoika1
1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Institute for Cancer Research, Medical University of Vienna, Austria;
3National University Lviv Polytechnic, Ukraine;
4Ivan Franko Lviv National University, Ukraine;
Development of novel nanoscale functionalized carriers is nowadays one of the most urgent problems in cancer treatment.
The aim of our study was to compare the antineoplastic effect of free doxorubicin and its complex with a nanoscale polymeric carrier towards HTC116 colorectal carcinoma cells. It was established that application of the complex of poly(5-tret-butylperoxy)-5-methyl-1-hexene-3-in-co-glycydyl metacrylat)-graft-polyethyleneglycol (poly(VEP-GMA-PEG)-graft-PEG), where VEP – 5-tret-butylperoxy)-5-methyl-1-hexene-3-in; GMA – glycydyl metacrylat; graft-PEG – graft-polyethyleneglycol accordingly, functionalized with phosphatidylcholine for doxorubicin delivery increased 10 times the efficiency of cytotoxic action of this drug, as compared wich such efficiency in case of the action of free doxorubicin. The encapsulated form of doxorubicin caused more intensive cleavage of the reparation enzyme PARP and longer delay in G2/M cell cycle arrest, compared to such effects of free doxorubicin. The developed carrier itself is non-toxic to the used mammalian cells and does not cause impairment in their cell cycle. A deletion in both alleles of p53 gene did not affect the antineoplastic action of doxorubicin that was immobilized on the nanoscale carrier. Thus, p53-dependent signaling pathways are not involved in the cytotoxic action of doxorubicin-carrier complex. It is suggested that novel nanoscale polymeric carrier poly(VEP-GMA-PEG)-graft-PEG functionalized with phosphatidylcholine could be a promising carrier for targeted delivery of anticancer drugs.
Key words: human colorectal carcinoma cells, doxorubicin, nanoscale polymeric drug carrier, cell cycle, PARP, apoptosis.
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