Abstract
Surgery is the preferred treatment for colorectal cancer, and the preoperative radiotherapy (pre-RT) improves surgical success and postoperative quality of life for patients. However, the therapeutic effect of pre-RT is limited by radiation resistance of tumor and radiation susceptibility of intestine, probably resulting in poor tumor suppression and postoperative anastomotic injury. Herein, we select carboxymethyl chitosan (CMCS) to complex with cerium oxide (CeO2) and calcium ion (Ca2+), obtaining CMCS/CeO2&Ca nano-enema for the optimized pre-RT of colorectal cancer. CMCS/CeO2 and CMCS/CeO2&Ca can mop up various kinds of reactive oxygen species (ROS) and decomposes H2O2 that largely exists in tumor tissue into OH and oxygen (some OH in acidic environment and main oxygen in neutral environment), enhancing free radical clearance in normal tissue and radiation sensitivity of tumor. Meanwhile, RT-induced M1 macrophage in intestinal tissue and the proportion of M2 macrophages in X-rays-treated tumor could be reduced, owing to CMCS/CeO2&Ca-induced change of ROS level. Moreover, CMCS/CeO2&Ca could also promote the proliferation of stem cells in intestine. Therefore, CMCS/CeO2&Ca improves the radio-immunotherapy outcome of colorectal cancer and reduces RT-induced intestinal inflammation/fibrosis, providing an optimal scheme and an effective enema for pre-RT for colorectal cancer.
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