Laboratory of Mechanisms of Drug Resistance, R.E. Kavetsky Institute for Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine.
Faculty of Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Int J Nanomedicine. 2024 Nov 11;19:11719-11743. doi: 10.2147/IJN.S485106. eCollection 2024.
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 Zn into the cytosol occurs in 2-3 hours 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.
肿瘤耐药性和全身毒性是现代抗癌治疗的主要挑战。纳米技术使创造具有抗癌治疗所需特性的新材料成为可能。
在这项研究中，使用了葡聚糖接枝-聚丙烯酰胺/氧化锌纳米粒子。研究使用前列腺（DU-145、LNCaP、PC-3）、乳腺癌（MDA-MB-231、MCF-7、MCF-7 Dox）癌细胞和非恶性（MAEC、BALB/3T3 clone A31）细胞进行。体外和体内用荧光可视化锌。通过细胞术鉴定 ROS 和凋亡标志物。在大鼠模型中评估锌在肿瘤、肝、肾和脾中的积累和组织病理学变化。
ZnO 纳米粒子在 2-3 小时内解离并将 Zn 释放到细胞质中，在癌细胞和非癌细胞中均发生。所有细胞中均检测到 ROS 上调。对于非恶性细胞，初始 ROS 水平的差异不显著。纳米系统降低了癌细胞中的碳水化合物代谢率。用纳米系统和阿霉素联合处理后，肿瘤中的锌水平分别上调了 25%和 39%。与对照组相比，单用纳米复合物和 65 倍低时，Walker-256 癌肉瘤肿瘤体积减小了两倍。在肝、肾和脾中，锌水平增加了 10-15%，但组织中未检测到明显的病理改变。
D-PAA/ZnO NPs 纳米系统通过内吞作用在短时间内被前列腺癌、乳腺癌细胞和非恶性细胞内化，但在体外和体内对非恶性细胞的细胞毒性明显较低。D-PAA/ZnO NPs 纳米复合物有效地促进了肿瘤细胞的死亡，而对非恶性细胞没有显示出细胞毒性，使其成为一种有前途的抗癌药物。
