D-π-A sensitized carbon dots as long-lived type-I/Ⅱ photosensitizers for NIR-excited hypoxia-regulated photodynamic therapy

In the development of clinically translatable triplet photosensitizers for hypoxia regulated photodynamic therapy (PDT), there is an unmet need for engineering sensitizers as near-infrared (NIR)-responsive, type I/type Ⅱ dual photosensitizers and mild photothermal agents. Herein, we develop a binary precursor-engineering strategy for precise regulation of the D-π-A configuration of carbon dots (CDs) as ultralong-lived triplet, type I/Ⅱ dual photosensitizers by utilizing phenolic hydroxyl as an electron-rich donor and pyridine N as an electron-withdrawing acceptor. The photodynamic performance of CDs is enhanced by intramolecular charge transfer and mild photothermal conversion. We further design M1-like macrophage-derived cell membrane‑camouflaged CDs to realize preferential tumor accumulation while guaranteeing rapid systemic clearance. D-π-A sensitized CD-mediated PDT induces anti-tumor activity against primary and distant tumors. Our work highlights the crucial roles of D-π-A sensitization of CDs in boosting PDT by triplet state tuning, surface charge transfer, and mild photothermal relief of hypoxia. The properties of small-sized carbon dots have been exploited to generate theranostic agents for bioimaging and imaging-guided cancer therapies. Here the authors report the design and characterization of D-π-A sensitized carbon dots for type-I/II photodynamic therapy (PDT), showing PDT-induced anti-tumor activity in preclinical models.