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.