De Novo Design of Reversibly pH-Switchable NIR-II Aggregation-Induced Emission Luminogens for Efficient Phototheranostics of Patient-Derived Tumor Xenografts

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Abstract

Phototheranostics has received sustained attention due to its great potential in revolutionizing conventional strategies of cancer treatment. However, trapped by the complexity, poor reproducibility, insufficient phototheranostic outputs, and inevitable damage to normal tissue of most multicomponent phototheranostic systems, its clinical translation has been severely hindered. Therefore, the exploration of "one for all" smart phototheranostic agents with versatile functionalities remains an appealing yet enormously challenging task. Herein, a reversibly pH-switchable and near-infrared second photosensitizer featuring aggregation-induced emission was tactfully designed by molecular engineering for precise tumor-targeting fluorescence imaging-guided phototherapy. Thanks to the strong intramolecular charge transfer, enhanced highly efficient intersystem crossing, and sufficient intramolecular motion, the developed agent DTTVBI was endowed with boosted type-I superoxide anion radical generation and excellent photothermal performance under 808 nm laser irradiation. More importantly, DTTVBI nanoparticles with high biocompatibility exhibit remarkably enhanced type-I photodynamic/photothermal therapy in the tumor region, thus offering significant antitumor effects both in vitro and in the patient-derived tumor xenograft model of colon cancer. This work sheds new light on the development of superior versatile phototheranostics for cancer therapy.

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