Dextran-Graft-Polyacrylamide/Zinc Oxide Nanoparticles Inhibit of Cancer Cells in vitro and in vivo.

Abstract

Tumor drug resistance and systemic toxicity are major challenges of modern anticancer therapy. Nanotechnology makes it possible to create new materials with the required properties for anticancer therapy. In this research, Dextran-graft-Polyacrylamide/ZnO nanoparticles were used. The study was carried out using prostate (DU-145, LNCaP, PC-3), breast (MDA-MB-231, MCF-7, MCF-7 Dox) cancer cells and non-malignant (MAEC, BALB/3T3 clone A31) cells. Zinc was visualized with fluorescence in vitro and in vivo. ROS and apoptotic markers were identified by cytometry. Zinc accumulation and histopathological changes in the tumor, liver, kidney, and spleen were evaluated in a rat model. ZnO nanoparticles dissociation and release of Zn2+ into the cytosol occurs in 2-3hours for cancerous and non-cancerous cells. ROS upregulation was detected in all cells. For non-malignant cells, the difference between the initial ROS level was insignificant. The rate of carbohydrate metabolism in cancer cells was reduced by nanosystems. Zinc level in the tumor was upregulated by 25% and 39% after treatment with nanosystems and doxorubicin combined, respectively. The tumor Walker-256 carcinosarcoma volume was reduced twice following mono-treatment with the nanocomplex and 65-fold lower when the nanocomplex was combined with doxorubicin compared with controls. In the liver, kidney and spleen, the zinc level increased by 10-15% but no significant pathological alterations in the tissues were detected. D-PAA/ZnO NPs nanosystems were internalized by prostate, breast cancer cells and non-malignant cells via endocytosis after short time, but cytotoxicity against non-cancer cells were significantly lower in vitro and in vivo. D-PAA/ZnO NPs nanocomplex efficiently promoted cell death of tumor cells without showing cytotoxicity against non-malignant cells making it a promising anti-cancer agent.