Cell Membrane Coated Semiconducting Polymer Nanoparticles for Enhanced Multimodal Cancer Phototheranostics

Phototheranostic nanoagents are promising for early diagnosis and precision therapy of cancer. However, their imaging ability and therapeutic efficacy are often limited due to the presence of delivery barriers in the tumor microenvironment. Herein, we report the development of organic multimodal phototheranostic nanoagents that can biomimetically target cancer-associated fibroblasts in the tumor microenvironment for enhanced multimodal imaging-guided cancer therapy. Such biomimetic nanocamouflages comprise a near-infrared (NIR) absorbing semiconducting polymer nanoparticle (SPN) coated with the cell membranes of activated fibroblasts. The homologous targeting mechanism allows the activated fibroblast cell membrane coated SPN (AF-SPN) to specifically target cancer-associated fibroblasts, leading to enhanced tumor accumulation relative to the uncoated and cancer cell membrane coated counterparts after systemic administration in living mice. As such, AF-SPN not only provides stronger NIR fluorescence and photoacoustic signals to detect tumors but also generates enhanced cytotoxic heat and singlet oxygen to exert combinational photothermal and photodynamic therapy, ultimately leading to an antitumor efficacy higher than that of the counterparts. This study introduces an organic phototheranostic system that biomimetically targets the component in the tumor microenvironment for enhanced multimodal cancer theranostics.