Photo-decomposable Organic Nanoparticles for Combined Tumor Optical Imaging and Multiple Phototherapies

Combination of photodynamic therapy (PDT) with photothermal therapy (PTT) has achieved significantly improved therapeutic efficacy compared to a single phototherapy modality. However, most nanomaterials used for combined PDT/PTT are made of non-biodegradable materials (e.g., gold nanorods, carbon nanotubes, and graphenes) and may remain intact in the body for long time, raising concerns over their potential long-term toxicity. Here we report a new combined PDT/PTT nanomedicine, designated SP³NPs, that exhibit photo-decomposable, photodynamic and photothermal properties. SP³NPs were prepared by self-assembly of PEGylated cypate, comprising FDA-approved PEG and an ICG derivative. We confirmed the ability of SP³NPs to generate both singlet oxygen for a photodynamic effect and heat for photothermal therapy in response to NIR laser irradiation in vitro. Also, the unique ability of SP³NPs to undergo irreversible decomposition upon NIR laser irradiation was demonstrated. Further our experimental results demonstrated that SP³NPs strongly accumulated in tumor tissue owing to their highly PEGylated surface and relatively small size (~60 nm), offering subsequent imaging-guided combined PDT/PTT treatment that resulted in tumor eradication and prolonged survival of mice. Taken together, our SP³NPs described here may represent a novel and facile approach for next-generation theranostics with great promise for translation into clinical practice in the future.