Co-encapsulated with shikonin/doxorubicin pH-sensitive liposomes: Preparation, characterization and its synergistic effect in drug-resistant breast cancer cells.

The present study was designed to prepare co-encapsulated with shikonin/doxorubicin pH-sensitive liposomes (SHK/DOX-pHSL) and investigate their synergistic anti-cancer effect in drug-resistant breast cancer cells. SHK/DOX-pHSL exhibited a mean diameter of around 145 nm, with a polydispersity index about 0.25. SHK/DOX-pHSL displayed high encapsulation efficiency, good colloidal stability, and sustained-release property. The cumulative release rates of DOX and SHK from SHK/DOX-pHSL were significantly higher in pH 5.0 than those in pH 7.4. In vitro the results showed that SHK/DOX-pHSL could inhibit cell proliferation, migration, invasion, and promoting cell apoptosis. The further studies revealed that SHK/DOX-pHSL could significantly promote cell apoptosis by regulating the expression of Bax and Bcl-2. Moreover, SHK/DOX-pHSL could reverse multidrug resistance (MDR) in MCF-7/ADR cells by inhibiting the expression of MDR1, ABCG2, and MRP1. SHK/DOX-pHSL was successfully prepared and possessed good physical characteristics, which had strong synergistic anti-cancer efficacy and reversed MDR effect in breast cancer cells. Therefore, the novel co-loaded drugs liposomes can provide the basis for further in vivo anti-cancer experiments.