1.A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer.
Kun WANG ; Cong WANG ; Hange YANG ; Gong CHEN ; Ke WANG ; Peihong JI ; Xudong SUN ; Xuegong FAN ; Jie MA ; Zhencun CUI ; Xingkai WANG ; Hao TIAN ; Dengfu WU ; Lu WANG ; Zhimin WANG ; Jiangyan LIU ; Juan YI ; Kuan HU ; Hailong ZHANG ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(10):4995-5009
Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8+ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.
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