The therapy of triple‐negative breast cancer (TNBC) relies on chemotherapy basing on cytotoxic agents, including paclitaxel (PTX). Unfortunately, PTX will facilitate the invasion of cancer cells and the formation of metastases. To counteract pro‐metastasis of PTX in TNBC therapy, in this work, calcitriol (CTL) is delivered along with PTX by a dual‐pH‐sensitive micelle. The PTX/CTL‐co‐loaded dual‐pH‐sensitive micelle (PCDM) can switch its surface charge from negative to positive at the tumor tissue and release PTX and CTL inside the lysosomes because of the structure change of the polymers composing PCDM under the acidic condition. This property makes PCDM able to escape from mononuclear‐phagocyte system clearance and easy to enter tumor cells. PCDM efficiently suppresses the 4T1 primary tumor growth in mice and inhibits lung metastasis, due to downregulation of matrix metalloproteinase‐9 and BCL‐2 levels, upregulation of E‐cadherin level, and counteracting the PTX‐induced elevation of C‐C motif chemokine ligand 2 (CCL2) and Ly6C⁺ monocytes levels by CTL. PCDM shows good biocompatibility without promoting the serum calcium level. Therefore, the combination of PTX and CTL based on this pH‐sensitive micelle is promising for the TNBC treatment.

中文翻译：

---

骨化三醇负载的双pH敏感胶束抵消了紫杉醇在三阴性乳腺癌治疗中的促转移作用。

三阴性乳腺癌（TNBC）的治疗依赖于基于细胞毒性剂的化疗，包括紫杉醇（PTX）。不幸的是，PTX将促进癌细胞的侵袭和转移的形成。为了抵消TNBC治疗中PTX的前转移，在这项工作中，钙三醇（CTL）与PTX通过双pH敏感的胶束一起递送。PTX / CTL负载的双pH敏感胶束（PCDM）可以在肿瘤组织处将其表面电荷从负电荷切换为正电荷，并在溶酶体内释放PTX和CTL，这是由于在PCA下组成PCDM的聚合物的结构发生了变化。酸性条件。这种特性使PCDM能够逃脱单核吞噬细胞系统的清除，并易于进入肿瘤细胞。PCDM有效抑制小鼠的4T1原发性肿瘤生长并抑制肺转移，CTL ⁺单核细胞水平。PCDM在不提高血清钙水平的情况下显示出良好的生物相容性。因此，基于这种对pH敏感的胶束的PTX和CTL的结合有望用于TNBC处理。