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.

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