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.