RESUMO
Colorectal cancer is one of the most common malignant tumors in the world, and its treatment strategies mainly include surgical resection, chemotherapy, adjuvant radiotherapy, and immunotherapy. Among them, chemotherapy inevitably produces systemic toxicity due to the lack of tumor targeting properties and drug resistance caused by long-term medication frequently occurs, immensely constraining the efficacy of chemotherapy alone. To solve the above-mentioned problems, rhamnolipid was used to encapsulate the chemotherapeutic drug 5-FU and photothermal agent bismuthene nanosheets (BiNS), chitosan was applied as the shell of the nanoparticle, and BiNS@RHL-CS/5-FU NPs for oral administration was successfully prepared. When transported in the stomach and small intestine, the double protection of rhamnolipid and chitosan shell prevented the early release of BiNS and 5-FU. When transported to the colon, ß-glycosidase existing in the microenvironment along with elevated pH degraded the chitosan shell, and the reduction in particle size was beneficial for tumor tissue to uptake nanoparticles, thus greatly improving the tumor targeting ability of 5-FU and reducing the systemic toxicity. Due to the presence of BiNS, 1.0 W cm-2 808 nm laser irradiation significantly increased the temperature of the tumor site, not only killing tumor cells directly but also promoting cell uptake and penetration of nanoparticles in the tumor tissue, accelerating the release of 5-FU and improving the sensitivity of tumor cells to chemotherapy, eventually solving the shortcomings of traditional chemotherapy alone. Excellent anti-tumor efficacy has been achieved in both in vitro and in vivo experiments.