Background: Chemo-radiotherapy is the combined chemotherapy and radiotherapy on tumor treatment to obtain the local radiosensitization and local cytotoxicity of the tumor and to control the microscopic metastatic disease. Methods: In this study, 7-ethyl-10-hydroxycamptothecin (SN38) molecules could be successfully loaded into human serum albumin (HSA)–hyaluronic acid (HA) nanoparticles (SH/HA NPs) by the hydrophobic side groups of amino acid in HSA. Results: HSA could be used to increase the biocompatibility and residence time of the nanoparticles in the blood, whereas HA could improve the benefits and overall treatment effect on CD44-expressing colorectal cancer (CRC), and reduce drug side effects. In addition to its role as a chemotherapeutic agent, SN38 could be used as a radiosensitizer, able to arrest the cell cycle, and allowing cells to stay in the G2/M stage, to improve the sensitivity of tumor cells to radiation. In vivo results demonstrated that SH/HA NPs could accumulate in the tumor and produce significant tumor suppression, with no adverse effects observed when combined with γ-ray irradiation. This SH/HA NPs-medicated chemo-radiotherapy could induce an anti-tumor immune response to inhibit the growth of distal tumors, and produce an abscopal effect. Conclusions: Therefore, this SN38-loaded and HA-incorporated nanoparticle combined with radiotherapy may be a promising therapeutic artifice for CRC in the future.
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