Engineered Exosome-Mediated Near-Infrared-II Region V₂C Quantum Dot Delivery for Nucleus-Target Low-Temperature Photothermal Therapy

The limited penetration depth of photothermal agents (PTAs) active in the NIR-I biowindow and the thermoresistance caused by heat shock protein (HSP) significantly limit the therapeutic efficiency of photothermal therapy (PTT). To address the problem, we introduce a strategy of low-temperature nucleus-targeted PTT in the NIR-II region achieving effective tumor killing by combining the vanadium carbide quantum dots (V 2 C QDs) PTA and an engineered exosomes (Ex) vector. The small fluorescent V 2 C QDs with good photothermal effect in the NIR-II region were modified with TAT peptides and packaged into Ex with RGD modification (V 2 [email protected] ). The resulting nanoparticles (NPs) exhibited good biocompatibility, long circulation time, and endosomal escape ability, and they could target the cell and enter into the nucleus to realize low-temperature PTT with advanced tumor destruction efficiency. The fluorescent imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capability of the NPs were also revealed. The low-temperature nucleus-targeted PTT in the NIR-II region provides more possibilities toward successful clinical application of PTT.