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.

Automated summary

This study presents a new design of p-n junction sonosensitizers for enhanced sonodynamic therapy (SDT) of tumors. The sonosensitizer combines partially oxidized LiFePO4 nanorods and renal-clearable n-type N-doped CDs (N-CDs) to achieve effective spatial separation of electron-hole pairs generated by ultrasound, resulting in enhanced SDT effects. The constructed sonosensitizer exhibits high efficiency in generating reactive oxygen species, consuming free radicals, and reacting with overexpressed GSH. Additionally, the sonosensitizer can be safely eliminated from the body through renal clearance after completion of the SDT treatment.