A biodegradable p-n junction sonosensitizer for tumor microenvironment regulating sonodynamic tumor therapy

It is important yet challenging to develop a class of biocompatible semiconductor heterojunction sonosensitizers with enhanced charge carrier separation dynamics and tumor microenvironment (TME) regulating capability. Considering its p-type conductivity, Fe2+/Fe3+-based TME regulating capability, and biodegradability of an olivine iron phosphate, we presented a new sonosensitizer design by p-n junction engineering of partially oxidized LiFePO4 nanorods and renal-clearable n-type N-doped CDs (N-CDs) to achieve the effective spatial separation of the US-generated electron-hole pairs for enhanced sonodynamic therapy (SDT) of tumors. The constructed N-CD@LiFePO4 p-n junction sonosensitizer was found to exhibit high-efficiency 1O2 generation, Fe2+ catalyzed center dot OH production, and Fe3+-oxidized consumption of overexpressed GSH. The Fe2+ catalyzed H2O2 decomposition efficiency of N-CD@LiFePO4 was much higher than previously reported Fe3O4 nano-enzymes owing to the presence of (PO4)3- polyanions. Moreover, LiFePO4 was slowly degraded into non-toxic species of Li+, Fe3+, and PO43- while ultrasmall N-CDs were released from the composite for renal elimination, enabling the nanosonosensitizer to be harmlessly cleared out of the body after completion of SDT-based tumor eradication by single drug injection and single ultrasound (US) irradiation. The rationally designed p-n junction sonosensitizers could promote their SDT translation because of component biocompatibility, p-n junction configuration, and Fe2+/Fe3+ mediated TME regulation.