Mannose modified zwitterionic polyester-conjugated second near-infrared organic fluorophore for targeted photothermal therapy.

Cancer resistance has been the huge challenge to clinical treatment. A photothermal therapy of second near-infrared (NIR-II) organic dye small molecule has been used to conquer the cancer resistance. However, the available NIR-II dye lacks selectivity and spreads throughout the body. It has toxicity and indiscriminate burn injuries normal cells and tissues during therapy. Hence, to improve the therapeutic outcomes, herein, for the first time, we report the mannose-modified zwitterionic nanoparticles loading IR1048 dye, aiming to overcome cancer cellular resistance. The targeting molecule mannose has been applied to modify zwitterionic polyester, and the obtained polyester is employed to load IR1048 to prolong the circulation time in the blood and improve the stability of loaded dye, due to the good cytocompatibility of polyester and the antifouling properties of zwitterions. In vitro experimental results show that the pH-responsive targeted nanoparticles display satisfactory photophysical properties, prominent photothermal conversion efficiency (44.07%), excellent photothermal stability, negligible cytotoxicity for normal cells and strong photothermal toxicity to drug-resistant cancer cells. Moreover, due to the mannose targeting effect, cancer cells can endocytose the nanoparticles effectively. All these results demonstrate potential application of this alternative hyperthermal delivery system with remote-controllable photothermal therapy of tumor for accurate diagnosis by NIR-II fluorescence imaging.

Sex-dependent effects on gut microbiota regulate hepatic carcinogenic outcomes.

Emerging evidence points to a strong association between sex and gut microbiota, bile acids (BAs), and gastrointestinal cancers. Here, we investigated the mechanistic link between microbiota and hepatocellular carcinogenesis using a streptozotocin-high fat diet (STZ-HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) murine model and compared results for both sexes. STZ-HFD feeding induced a much higher incidence of HCC in male mice with substantially increased intrahepatic retention of hydrophobic BAs and decreased hepatic expression of tumor-suppressive microRNAs. Metagenomic analysis showed differences in gut microbiota involved in BA metabolism between normal male and female mice, and such differences were amplified when mice of both sexes were exposed to STZ-HFD. Treating STZ-HFD male mice with 2% cholestyramine led to significant improvement of hepatic BA retention, tumor-suppressive microRNA expressions, microbial gut communities, and prevention of HCC. Additionally the sex-dependent differences in BA profiles in the murine model can be correlated to the differential BA profiles between men and women during the development of HCC. These results uncover distinct male and female profiles for gut microbiota, BAs, and microRNAs that may contribute to sex-based disparity in liver carcinogenesis, and suggest new possibilities for preventing and controlling human obesity-related gastrointestinal cancers that often exhibit sex differences.