Cisplatin-Rubusoside Nanomicelles Improves Anti-Cancer Activity of Cisplatin against Multi-Drug-Resistant Breast Cancer Cells by Upregulating p21

Cisplatin (Cis) is employed as a 1L treatment for breast cancer. However, its therapeutic success is often limited by the emergence of resistance, which poses a significant barrier to effective disease management. Towards this challenge, we have engineered nanomicelles composed of cisplatin and rubusoside (Cis-Rub) as a novel drug delivery system. The formulated Cis-Rub nanomicelles exhibited a uniform size distribution, with an average diameter of around 32 nanometers. Uptake kinetic studies in MCF-7/Adr cells showed that Cis-Rub nanomicelles improved the cellular uptake of Cis by four-fold. In vitro cell viability studies demonstrated that the IC50 of Cis-Rub in MDA-MB-231 and MCF-7/Adr cells was lower than of Cis, indicating greater potency. Furthermore, to understand the mechanism of action, we performed flow cytometry and western blot analysis. Cis-Rub nanomicelles induced apoptosis in 42.17% of cells, while Cis induced apoptosis in only 10.17%. We also found that Cis-Rub increased the expression of p21. These findings indicate that Cis-Rub enhances the anticancer efficacy of cisplatin against drug-resistant breast cancer cells and may represent a more effective strategy for cancer therapy.