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Semiconducting polymer nanoparticles (SPNs) have shown great promise in second near-infrared window (NIR-II) phototheranostics. However, the issue of long metabolic time significantly restricts the clinical application of SPNs. In this study, we rationally designed a biodegradable SPN (BSPN50) for NIR-II fluorescence imaging-guided photodynamic therapy (PDT). BSPN50 is prepared by encapsulating a biodegradable SP (BSP50) with an amphiphilic copolymer F-127. BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole (DPP) segment and degradable poly(phenylenevinylene) (PPV) segment with the ratio of 50/50. BSPN50 has both satisfactory degradability under myeloperoxidase (MPO)/hydrogen peroxide (H2O2) and NIR-II fluorescence emission upon 808 nm laser excitation. Furthermore, BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation. BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo. In addition, BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT. Thus, our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.

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