Oxygen self-supplied nanoparticle for enhanced chemiexcited photodynamic therapy

Photodynamic therapy (PDT) is a promising strategy for effective cancer treatment. However, it still faces severe challenges, including poor laser penetration and insufficient oxygen (O₂) in solid tumors. Here, we constructed intelligent O₂self-supplied nanoparticles (NPs) for tumor hypoxia relief as well as effective chemiexcited PDT. Oxygen-carrying NPs (BSA@TCPO NPs) were obtained via the self-assembly of bovine serum albumin (BSA), bis[3,4,6-trichloro2-(pentyloxycarbonyl)phenyl]oxalate (TCPO), perfluorohexane (PFH), and chlorin e6 (Ce6). In H₂O₂-overexpressed tumor cells, TCPO in the NPs reacted with H₂O₂, releasing energy to activate the photosensitizer Ce6 and generate cytotoxic singlet oxygen (¹O₂) to kill tumor cells in a laser irradiation-independent manner. Moreover, the O₂carried by PFH not only reduced therapeutic resistance by alleviating tumor hypoxia but also increased¹O₂generation for enhanced chemiexcited PDT. The remarkable cytotoxicity to various cancer cell lines and A549 tumors demonstrated the advantage of BTPC in alleviating the hypoxic status and inhibiting tumor growth. Our results demonstrate that BTPC is a promising nanoplatform for cancer therapy.