Oxygen Self-Supplying Enzymatic Nanoplatform for Precise and Enhanced Photodynamic Therapy

Traditional oxygen-dependent photodynamic therapy (PDT) faces formidable challenges owing to abnormal angiogenesis and insufficient oxygen supply in solid tumors. Herein, a multifunctional nanoplatform (HRP-DPBF-Zn) consisting of photosensitizer zinc (II) phthalocyanine (ZnPc), singlet oxygen ( 1 O 2 ) probe 1,3-diphenylisobenzofuran (DPBF), and hydrogen peroxide (H 2 O 2 ) catalyst horseradish peroxidase (HRP) is developed. Such HRP-DPBF-Zn nanosystems are expected to possess catalase-like capacity for catalyzing intracellular H 2 O 2 to produce oxygen (O 2 ). The enhanced O 2 content further facilitates the production of cytotoxic 1 O 2 by ZnPc under laser irradiation. DPBF loading endows the nanoplatform with the high 1 O 2 sensitivity, which can promote precise PDT with fluorescent 1 O 2 feedback. HRP-DPBF-Zn exhibits excellent biocompatibility, efficient 1 O 2 generation, high 1 O 2 sensitivity, favorable H 2 O 2 -to-O 2 decomposition, and superior fluorescence imaging properties. Both in vitro and in vivo experimental results confirm that such HRP-DPBF-Zn can accomplish highly specific and efficient PDT against hypoxic tumors, which shows great potential in tumor theranostics.