癌症化疗面临两个主要挑战—活性物质的高毒性和肿瘤对药物的抗药性。低毒性纳米载体与抗癌药物的结合可以显著提高治疗效果。纳米技术的现代进展使得创建具有必要物理和化学性质的材料变得容易。在锌硫酸盐(D-PAA/ZnO NPs (SO42-))和乙酸锌(D-PAA/ZnO NPs (-OAc))的水溶液中合成了两种壳聚糖-聚丙烯酰胺/氧化锌纳米颗粒的混合纳米系统。使用光吸收、荧光、动态光散射和透射电子显微镜对纳米复合材料进行表征。MTT、中性红吸收和划痕实验被选为成纤维细胞细胞毒性测定的方法。在正常成纤维细胞、MAEC、前列腺(LNCaP、PC-3、DU-145)和乳腺(MDA-MB-231、MCF-7)癌细胞系中进行了体外细胞毒性测试。采用免疫细胞化学方法检测Ki-67、p53、Bcl-2、Bax、E-钙粘蛋白、N-钙粘蛋白和CD44的表达。使用乙酸基橙检测细胞的形态学变化。ZnO NPs (SO42-)的半径为1.5nm，ZnO NPs (-OAc)的半径为2nm。纳米系统对成纤维细胞和MAEC的毒性较低。所有研究的癌细胞系中发现了处于凋亡最后阶段并形成凋亡小体的细胞。癌细胞中的促凋亡蛋白表达表明凋亡性死亡。癌细胞系LNCaP、PC-3、DU-145和MCF-7在与D-PAA/ZnO NPs (SO42-)孵育48小时后，E-钙粘蛋白和N-钙粘蛋白的表达显著增加。纳米系统对成纤维细胞和MAEC的毒性较低。使用硫酸锌合成的D-PAA/ZnO NPs纳米系统通过破坏不同类型的癌细胞在体外显示出高细胞毒性，并潜在地增加细胞之间的粘附。因此，我们的研究结果表明D-PAA/ZnO NPs对癌细胞具有选择性细胞毒性，并有望用于癌症治疗。© 2023 Chumachenko et al.

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.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.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-).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.© 2023 Chumachenko et al.