化疗联合免疫治疗有望在肿瘤清除、抑制转移和预防复发方面发挥理想效果，但其协同抗肿瘤作用与肿瘤微环境息息相关。然而，如何针对肿瘤微环境特性而构建免疫和化疗药物共输送载体，分别靶向免疫和肿瘤细胞，实现真正意义上的协同增效仍面临极大挑战。本项目拟构建具有精确靶向递送特性、联合化疗免疫的肿瘤原位自组装药物多肽载体体系，利用甲酰肽受体激动剂多肽靶向肿瘤，并在肿瘤酶敏感环境下首先释放免疫药物，作用于肿瘤微环境中的免疫细胞；继而发生超分子自组装成纳米纤维产生聚集诱导停留效应，实现药物在肿瘤局部的富集和肿瘤细胞的高效摄取；载药纳米纤维进入肿瘤细胞后进一步通过还原和pH敏感特性释放化疗药物顺铂、抑制耐药和协同抗肿瘤作用的药物阿杜丁。相关研究将探索肿瘤微环境精确靶向性、肿瘤原位自组装特性、免疫和化疗药物逐级释放特性、化疗联合免疫途径全方位杀伤肿瘤的可行性和协同作用机制，为治疗甚至根除肿瘤提供创新性的研究思路。

With the increasingly sophisticated development of biology and medical science, there is mounting evidence to support that the appropriate combination of chemotherapy and immunotherapy can achieve synergetic antitumor effect to eradicate tumor, inhibit metastasis and prevent recurrence, and the synergism is closely related to the tumor microenvironment. However, it is still a great challenge to fabricate the chemo-immunotherapeutic drug codelivery system with consideration on the properties of tumor microenvironment which can target tumor and immune cells respectively and then realize the real synergistic effect. Therefore, in this project, we take advantage of precise targeting drug system to design a novel peptide-based delivery platform which can in-situ self-assemble to nanofiber in tumor microenvironment and release drugs spatiotemporally for chemo-immunotherapy. The targeting effect of formyl peptide receptor agonist W peptide in the formulation will promote the accumulation of drugs in tumor microenvironment. The immunotherapeutic drug will be first released under enzyme-responsive tumor microenvironment to activate antitumor immune response. At the same time, the enzyme cleaved peptide with cisplatin and adjudin conjugation will self-assemble to nanofiber with the assembly-induced retention effect, which can promote the drug retention and uptake by tumor cells. Subsequently, the conjugated drugs are able to be dissociated under intracellular reductive and pH-responsive environment to develop their synergistic antitumor and multidrug resistance inhibition effects. The drug delivery platform will realize the effective tumor killing through combination chemo-immunotherapy with the properties of precise targeting, in-situ self-assembly and spatiotemporal drug release in tumor microenvironment. It may provide a novel strategy for cancer treatment and complete tumor removal.