SN38-loaded nanomedicine mediates chemo-radiotherapy against CD44-expressing cancer growth

Abstract

Abstract 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.

Keywords

• Chemo-radiotherapy
• 7-Ethyl-10-hydroxycamptothecin
• Human serum albumin
• Hyaluronic acid
• Abscopal effect