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The indirect excitation of a photosensitizer mediated with nonlinear optical mechanism is a strategy for applying tissue penetration enhanced near infrared (NIR) light on photodynamic therapy (PDT). Herein, we introduced a NIR-PDT strategy that employed a nonlinear optical nano-conveyor named AHU-1 bearing strong second-harmonic generation (SHG) properties. AHU-1 could emit exactly half of the incident wavelengths for indirectly exciting the strong absorption soret band of the photosensitizers. Biocompatible micelles (mPEG–PDLLA) were applied to simultaneously encapsulate AHU-1 and photosensitizer, chlorin e6 (Ce6), for increasing their solubility and stability. The size and morphology of cargo loaded micelles were characterized by DLS and TEM. The cytotoxicity studies, live cell imaging and in situ photodynamic efficacy were conducted on B16 melanoma cells, and the SHG-mediated PDT effectively eliminated the cancer cells. This study provides a novel strategy for the application of nonlinear optical materials in photodynamic therapy.

In situ second-harmonic generation mediated photodynamic therapy by micelles co-encapsulating coordination nanoparticle and photosensitizer