Doxorubicin-Loaded Redox-Responsive Polymeric Nanomicelles Delivery System to Reverse Multidrug Resistance in Drug-Resistant Breast Cancer Cells

Objective. The objective of this work was to determine whether DOX-loaded P-5k SSLV can reverse MDR in MCF-7/Adr cells, with DOX solution and redox-insensitive P-5k LV-DOX nanomicelles as the controls. Methods. The cytotoxicity, cellular uptake and apoptosis of P-5k SSLV-DOX nanomicelles were investigated in MCF-7/Adr cells. The reverse factor (RF) values of P-5k SSLV-DOX following 48 h and 72 h incubation were also investigated. Key findings. The reverse factor (RF) values of P-5k SSLV-DOX following 48 h and 72 h incubation in MCF-7/Adr cells were 2.81 and 2.16, respectively. The P-5k SSLV-DOX nanomicelles enhanced the cytotoxicity of DOX significantly in breast cancer drug-resistant cells. Uptake studies with P-5k SSLV-DOX nanomicelles indicated that the nanomicelles significantly increased the level of drug accumulation in drug-resistant cells. Fluorescence microscopy studies demonstrated that DOX-loaded P-5k SSLV nanomicelles predominantly localized in the nucleus, whereas DOX in DOX solution and P-5k LV nanomicells accumulated mainly in the peripheral region. P-5k SSLV-DOX also showed increased apoptosis in MCF-7/Adr cells as compared with DOX solution and redox-insensitive P-5k LV-DOX nanomicelles. Conclusions. Taken together, these results highlight the promising application of P-5k SSLV-DOX nanomicelles to reverse drug resistance of cancer cells through fast intracellular drug release.