Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

Abstract

Vasyl Chumachenko,1 Pavlo Virych,1 Guochao Nie,2 Petro Virych,3 Oleg Yeshchenko,4 Pavlo Khort,4 Anton Tkachenko,5 Volodymyr Prokopiuk,5,6 Nataliia Lukianova,3 Taras Zadvornyi,3 Michel Rawiso,7 Liyao Ding,2 Nataliya Kutsevol1,7 1Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine; 2Guangxi Universities Key Laboratory of Complex System Optimization and Big Data Processing, Yulin Normal University, Yulin, People’s Republic of China; 3Laboratory of Mechanisms of Drug Resistance, R.E. Kavetsky Institute for Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine; 4Physics Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine; 5Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Kharkiv, Ukraine; 6Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine; 7Institut Charles Sadron, Strasbourg, FranceCorrespondence: Guochao Nie, Guangxi Universities Key Laboratory of Complex System Optimization and Big Data Processing, Yulin Normal University, Yulin, 537000, People’s Republic of China, Tel [phone], Email [email protected] Pavlo Virych, Chemistry Department, Taras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, 01601, Ukraine, Tel [phone], Email [email protected]: Cancer chemotherapy faces two major challenges – high toxicity of active substances and tumor resistance to drugs. Low toxic nanocarriers in combination with anticancer agents can significantly increase the effectiveness of therapy. Modern advances in nanotechnology make it easy to create materials with the necessary physical and chemical properties.Methods: Two hybrid nanosystems of dextran-polyacrylamide/ zinc oxide nanoparticles (D-PAA/ZnO NPs) were synthesized in aqueous solution with zinc sulphate (D-PAA/ZnO NPs (SO42-)) and zinc acetate (D-PAA/ZnO NPs (-OAc)). The light absorption, fluorescence, dynamic light scattering and transmission electron microscopy for nanocomposite characterization were used. MTT, neutral red uptake and scratch assays were selected as fibroblasts cytotoxicity assays. Cytotoxicity was tested in vitro for normal fibroblasts, MAEC, prostate (LNCaP, PC-3, DU-145) and breast (MDA-MB-231, MCF-7) cancer cells lines. Immunocytochemical methods were used for detection of Ki-67, p53, Bcl-2, Bax, e-cadherin, N-cadherin and CD44 expression. Acridine orange was used to detect morphological changes in cells.Results: The radius of ZnO NPs (SO42-) was 1.5 nm and ZnO NPs (-OAc) was 2 nm. The nanosystems were low-toxic to fibroblasts, MAEC. Cells in the last stages of apoptosis with the formation of apoptotic bodies were detected for all investigated cancer cell lines. Proapoptotic proteins expression in cancer cells indicates an apoptotic death. Increased expression of E-cadherin and N-cadherin was registered for cancer cells line LNCaP, PC-3, DU-145 and MCF-7 after 48 h incubation with D-PAA/ZnO NPs (SO42-).Conclusion: The nanosystems were low-toxic to fibroblasts, MAEC. The D-PAA/ZnO NPs nanosystem synthesized using zinc sulphate demonstrates high cytotoxicity due to destruction of various types of cancer cells in vitro and potentially increases adhesion between cells. Thus, our findings indicate the selective cytotoxicity of D-PAA/ZnO NPs against cancer cells and can be potentially used for cancer treatment.Keywords: zinc oxide nanoparticles, polymer nanocarrier, drug delivery, cytotoxicity, prostate cancer, breast cancer

Keywords

• zinc oxide nanoparticles
• polymer nanocarrier
• drug delivery
• cytotoxicity
• prostate cancer
• breast cancer