结直肠癌属于高度异质性疾病，且自身肿瘤免疫原性较低。提高个体化治疗效果，并进一步抑制肿瘤扩散和复发是结直肠癌治疗努力的方向。本课题基于pH敏感/DC靶向的Toll样受体7/8激动剂聚合物偶联体，协同光热敏感剂和化疗药物，构建分级定向递药系统主动启动抗肿瘤免疫，用于结直肠癌的个体化治疗。利用光热疗法杀伤原癌肿瘤细胞，辅以化疗药物杀死残余原癌细胞，协同诱导免疫原性细胞死亡，激发释放肿瘤相关抗原；采用TLR7/8激动剂增强树突状细胞抗原呈递，激活能够识别自体肿瘤抗原的特异性T细胞，激发肿瘤患者自身细胞免疫功能。拟利用中空硫化铜纳米粒作为光敏剂，同时作为载体荷载化疗药物奥沙利铂靶向肿瘤部位消除原癌肿瘤，荷载靶向树突状细胞的pH敏感免疫激动剂IMDQ-聚合物偶联体，在肿瘤组织分级定向并激活树突状细胞，通过增强机体免疫反应，有望抑制肿瘤的转移及复发，提高结直肠癌个体化治疗效果。

Colorectal cancer is a highly heterogeneous disease with low tumor immunogenicity and the direction of cancer treatment efforts is to improve the individualized treatment effect of colorectal cancer and further inhibit the metastasis and recurrence of cancer. This project, based on the pH sensitive and dendritic cells-targeted TLR7/8 agonist-polymer conjugate, constructs a graded directional drug delivery system with photothermal and chemotherapy to initiate anti-tumor immunity, which can be used in the individualized treatment of colorectal cancer. The system causes local tumor regression and eradication by chemo-photothermal therapy combination and stimulates immunogenic cell death and the release of tumor related antigens, while activates the specific T cells that can recognize the tumor antigens by inducing dendritic cells in vivo with TLR7/8 agonist, and stimulate the anti-tumor immune function of patients. It is proposed to use hollow copper sulfide nanoparticles as photosensitizer and as carrier for Oxaliplatin (OXA) to eliminate tumors and for pH sensitive IMDQ-polymer conjugate to target dendritic cells, thus achieving co-delivery as well as graded orientation of dual drugs and improving the treatment effect of colorectal cancer. By enhancing the immune response of the body, it is expected to inhibit the metastasis and recurrence of the tumor and improve the individualized treatment effect of colorectal cancer.