Dual-responsive smart nano-platform targeting peptide modifications synergistically enhances multimodal therapy for liver cancer

Abstract

Abstract The success of clinical therapies against liver cancer is largely determined the accuracy rate of treatment. Herein, we designed a dual-responsive smart nano-platform (HMCuS@DOX@9R-P201) could realize multimodal synergistic therapy. The nano-platform could precisely recognize the protein marker FOXM1c-DBD on the surface of HepG2 cells. The apoptosis rate of HepG2 cells reached 98.51% under near-infrared (NIR) laser irradiation, and the tumor inhibition rate of HMCD9P NPs + L treatment group was as high as 88.2% in mice. Moreover, it could up-regulate the apoptosis-related protein Bak, down-regulate PARP-1, Bcl-2, and Caspase 8, and inhibit the pathway protein FOXM1, thus down-regulating Skp2, up-regulate p27Kip1, and precise induction of multimodal synergistic therapy based on chemotherapy, PTT, and PDT to improve anti-HCC efficacy and reduce side effects. Overall, we report a liver cancer-targeted smart nano-platform with promising anti-liver cancer effects and multiple synergistic therapeutic mechanisms.