Semiconducting Polymer Nano-prodrug for Hypoxia-activated Synergetic Photodynamic Cancer therapy.

Photodynamic therapy (PDT) holds great promise for cancer therapy; however, its efficacy is often compromised by tumor hypoxia. We herein synthesize a semiconducting polymer nanoprodrug (SPNpd) that not only efficient generates singlet oxygen (1O2) under near-infrared (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) (PEG) and conjugated with the chemodrug molecules via hypoxia-cleavable linkers. Such a well-defined and compact nanostructure of SPNpd (30 nm) enables preferable accumulation in the tumor of living mice. By virtue of these molecular advantages, SPNpd exerts synergistic photodynamic and chemo-therapy, and effectively inhibit tumor growth in xenograft tumor mouse model, which is not possible for its prodrug-free counterpart. This study thus represents the first hypoxia-activatable phototherapeutic polymeric prodrug system with a high potential for cancer therapy.