Bioorthogonal NIR-IIb Quantum Dots for Imaging-Guided Photothermal Therapy

Improving the penetrating and targeting abilities of therapeutic agents in deep tumors remains the primary challenge for photothermal therapy (PTT). In this study, we propose a bioorthogonal targeting strategy combined with quantum dots (QDs) emitting in the near-infrared IIb window (NIR-IIb) for high-efficiency PTT of tumor. By injecting metabolic glycoengineering prodrugs, the bioorthogonal chemical receptor-azido groups were generated on the membrane tumor cells and then transported to adjacent cells in deep tumor through extracellular vesicles (EVs). Bioorthogonal NIR-IIb QDs modified with the dibenzocyclooctyne (DBCO) group penetrated into deep tumor and bound with cells through specific and irreversible click reaction, the bioorthogonal reaction between azido and DBCO groups, which significantly improved the targeting efficiency and retention time of QDs in the tumor. Guided by the fluorescence imaging in the NIR-IIb window with a high resolution, the accumulation of QDs at the tumor site was observed in real time to determine both the tumor location and the optimal radiation time for PTT treatment. Owing to the abundant QDs in deep tumor with a high photothermal conversion efficiency, remarkable therapeutic efficacy was achieved.