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

Mengmeng Zhang; Na Ying; Jie Chen; Liwen Wu; Huajie Liu; Shihua Luo; Dongdong Zeng

doi:10.1111/cpr.13603

Cell Proliferation ›› 2024, Vol. 57 ›› Issue (6) :e13603 DOI: 10.1111/cpr.13603

ORIGINAL ARTICLE

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

Mengmeng Zhang ¹^,²
, Na Ying ¹^,²
, Jie Chen ³
, Liwen Wu ¹
, Huajie Liu ³^,^†
, Shihua Luo ⁴^,^†
, Dongdong Zeng ¹^,^†

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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 pH-responsive polymeric micelles for co-delivery of PTX and TPL, which disassembling in acidic tumour microenvironments to target drug release and effectively kill breast cancer cells. Firstly, we synthesized amphiphilic copolymer mPEG₂₀₀₀-PBAE through Michael addition reaction, confirmed by various 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 PDI of 0.237 ± 0.003 and Zeta potential of 9.57 ± 0.80 mV, LC% was 6.19 ± 0.21%, EE% was 88.67 ± 3.06%. Carrier material biocompatibility and loaded micelle cytotoxicity were assessed using the CCK-8 method, demonstrating excellent biocompatibility. Under the same drug concentration, TPL/PTX-PMs were the most toxic to tumour cells and had the strongest proliferation inhibitory effect. Cellular uptake assays revealed that TPL/PTX-PMs significantly increased intracellular drug concentration and enhanced antitumor activity. Overall, pH-responsive micellar co-delivery of TPL and PTX is a promising approach for breast cancer therapy.

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Mengmeng Zhang, Na Ying, Jie Chen, Liwen Wu, Huajie Liu, Shihua Luo, Dongdong Zeng. Engineering a pH-responsive polymeric micelle co-loaded with paclitaxel and triptolide for breast cancer therapy. Cell Proliferation, 2024, 57(6): e13603 DOI:10.1111/cpr.13603

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