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A novel active mitochondrion-selective fluorescent probe for the NIR fluorescence imaging and targeted photodynamic therapy of gastric cancer.

The annual morbidity and mortality due to gastric cancer are still high across the world, posing a serious threat to public health. Improving the diagnosis rate of gastric cancer and exploring new treatments are urgent issues in the clinical field. In recent years, photosensitizer (PS)-based photodynamic therapy (PDT) has proven to be an effective cancer treatment strategy and can be used to treat a variety of cancers. Developing PSs with tumor-targeting ability and high singlet oxygen yield (Φ(1O2)) is the key to improving the PDT effect. Herein, we developed a novel diagnosis and treatment system (Cy1395-NPs). Our active thio-photosensitizer is based on the sulfur substitution strategy as it can reduce the S1-T1 energy gap, which can promote the process of intersystem crossing (ISC), thus resulting in high ROS generation efficiency. Cy1395-NPs exhibited stable spectral characteristics, satisfactory biocompatibility and high 1O2 yield under laser irradiation due to the introduction of the sulfur atom. In cellular studies, Cy1395-NPs could specifically target MKN45 cells via integrin αvβ3-mediated cRGD endocytosis and selectively aggregate in the mitochondria. Cy1395-NPs had no obvious cytotoxicity for MKN45 cells and exerted obvious phototoxicity due to the production of 1O2 under laser irradiation. The in vivo results showed that the fluorescence signal from the tumor site was obviously enhanced in 16-48 h, and Cy1395-NPs could selectively target solid tumors with a retention time of about 32 h. Under laser irradiation, Cy1395-NPs significantly inhibited tumor growth and led to significant tumor suppression and apoptosis. In summary, the developed Cy1395-NPs could actively target tumors and exert mitochondrial selectivity, showing an excellent fluorescence imaging effect. Under the irradiation of an 808 nm laser, Cy1395-NPs achieved good inhibition of gastric cancer cells both in vitro and in vivo, thus displaying the functions of tumor targeting, mitochondrial selectivity, fluorescence imaging and tumor inhibition. Our strategy provides a new diagnostic and treatment method for gastric cancers in clinical settings.