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Life sciences · Journal article
Acs Omega · October 14, 2026
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Abstract Tumor microenvironment is closely involved in breast cancer progression and metastatic spread. Therefore, it is essential to develop a combination therapy to suppress tumor progression by regulating TME. Herein, Ru486-loaded doxorubicin (DOX)–chondroitin sulfate (chondroitin sulfate) nanomicelles (R/D-CS) were prepared for combined delivery. A “MCF-7 + MRC-5” dual-cell model and “4T1 + NIH-3T3” cell-bearing mouse model were established to recapitulate TME in vitro and in vivo, respectively. Interestingly, R/D-CS nanomicelles internalized cancer-associated fibroblasts and tumor cells and reduced tumor proliferation and migration markedly by downregulating expression of P-gp, vimentin, and CXCR4. Moreover, the in vivo antitumor studies were performed on a tumor-bearing mouse model, R/D-CS nanomicelles showed stronger antiproliferative and antimetastatic effects. Overall, the combination therapy based on R/D-CS nanomicelles was potent for breast cancer treatment.