Covalent Organic Nanosheets Integrated Heterojunction with Two Strategies To Overcome Hypoxic-Tumor Photodynamic Therapy

Photodynamic therapy (PDT) still faces a key challenge associated with its oxygen-dependent property, which limits its therapeutic efficiency against hypoxic tumor. To address the problem, covalent organic nanosheets (CONs) are prepared with a donor–acceptor molecular heterostructure. CONs can address the hypoxic-tumor PDT by two strategies, that is, type I PDT and type I PDT combined with photothermal therapy (PTT). On the one hand, the molecular heterostructure of CONs can afford highly efficient charge carrier separation, a long lifetime of electrons and holes can be obtained, the electrons can reduce O 2 to form O 2 ·–, and at the same time, the holes can oxidize water to produce ·OH. Therefore, type I PDT is obtained, which can be used to diminish the limits of hypoxia in type II PDT. On the other hand, the recombination of photoexcited species results in an important nonradiative attenuation, and thus the energy is emitted as heat. A combination of type I PDT and PTT serves as an effective way to get around the difficulties of hypoxia in PDT. Intravenous injection of CONs in nude mice followed by the combination of type I PDT and PTT under single-wavelength irradiation achieves significant tumor ablation.