Oxygenic Hybrid Semiconducting Nanoparticles for Enhanced Photodynamic Therapy

Photodynamic nanotheranostics has shown great promise for cancer therapy; however, its therapeutic efficacy is limited due to the hypoxia of tumor microenvironment and the unfavorable bioavailability of existing photodynamic agents. We herein develop hybrid core–shell semiconducting nanoparticles (SPN-Ms) that can undergo O2 evolution in hypoxic solid tumor to promote photodynamic process. Such oxygenic nanoparticles are synthesized through a one-pot surface growth reaction and have a unique multilayer structure cored and coated with semiconducting polymer nanoparticles (SPNs) and manganese dioxide (MnO2) nanosheets, respectively. The SPN core serves as both NIR fluorescence imaging and photodynamic agent, while the MnO2 nanosheets act as a sacrificing component to convert H2O2 to O2 under hypoxic and acidic tumor microenvironment. As compared with the uncoated SPN (SPN-0), the oxygenic nanoparticles (SPN-M1) generate 2.68-fold more 1O2 at hypoxic and acidic conditions under NIR laser irradiation at 808 nm. Because of such an oxygen-evolution property, SPN-M1 can effectively eradicate cancer cells both in vitro and in vivo. Our study thus not only reports an in situ synthetic method to coat organic nanoparticles but also develops a tumor-microenvironment-sensitive theranostic nanoagent to overcome hypoxia for amplified therapy.