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.