A Semiconducting Polymer Nano‐prodrug for Hypoxia‐Activated Photodynamic Cancer Therapy

Abstract Photodynamic therapy (PDT) holds great promise for cancer therapy; however, its efficacy is often compromised by tumor hypoxia. Herein, we report the synthesis of a semiconducting polymer nanoprodrug (SPNpd) that not only efficiently generates singlet oxygen (1O2) under NIR photoirradiation but also specifically activates its chemotherapeutic action in hypoxic tumor microenvironment. SPNpd is self‐assembled from a amphiphilic polymer brush, which comprises a light‐responsive photodynamic backbone grafted with poly(ethylene glycol) and conjugated with a chemodrug through hypoxia‐cleavable linkers. The well‐defined and compact nanostructure of SPNpd (30 nm) enables accumulation in the tumor of living mice. Owing to these features, SPNpd exerts synergistic photodynamic and chemo‐therapy, and effectively inhibits tumor growth in a xenograft tumor mouse model. This study represents the first hypoxia‐activatable phototherapeutic polymeric prodrug system with a high potential for cancer therapy.