Engineering a pH-responsive polymeric micelle co-loaded with paclitaxel and tretinoin for breast cancer therapy

Abstract

Abstract Breast cancer has overtaken lung cancer as the number one cancer worldwide. Paclitaxel (PTX) is a widely used first-line anti-cancer drug, but it is not very effective in clinical breast cancer therapy. It has been reported that triptolide (TPL) can enhance the anticancer effect of paclitaxel, and better synergistic therapeutic effects are seen with concomitant administration of PTX and TPL. In this study, we developed a pH-responsive polymeric micelle co-delivery of PTX and TPL, which disassembled in the acidic microenvironment of tumors, leading to the targeted release of drugs that effectively kill breast cancer cells. Firstly, the amphiphilic copolymer mPEG2000-PBAE was synthesized by Michael addition reaction, and the successful synthesis of the copolymer was confirmed by a series of characterizations. Polymer micelles loaded with TPL and PTX (TPL/PTX-PMs) were prepared by the thin film dispersion method. The average particle size of TPL/PTX-PMs was 97.29 ± 1.63 nm, with a PDI of 0.237 ± 0.003 and a zeta potential of 9.57 ± 0.80 mV, LC% was 6.19 ± 0.21%, EE% was 88.67 ± 3.06%. The biocompatibility of carrier materials and cytotoxicity of drug-loaded micelles were evaluated in vitro by the CCK-8 method. The results showed that the carrier materials had excellent biocompatibility. Under the same drug concentration, TPL/PTX-PMs were the most toxic to tumor cells and had the strongest proliferation inhibitory effect. Cellular uptake assays showed that TPL/PTX-PMs significantly increased the intracellular concentration of the drugs and enhanced the antitumor activity. Overall, the co-delivery of TPL and PTX by the pH responsive micelles synthesized from amphiphilic copolymers is a promising approach for breast cancer therapy.