局部治疗是恶性肿瘤治疗的主要方法之一，然而治疗范围外的肿瘤迅速增长导致疾病进展。瘤内免疫作为局部治疗的一种手段，不仅对治疗局部有抗肿瘤作用，对肿瘤全身多发转移灶均有明显的抑制作用。本研究以生物相容性好、缓释性能佳的丝素蛋白为主要载体，以靶向和调节免疫分子功能的核酸适配体的筛选为基础，构建负载CpG ODN, CTLA-4 aptamer，PD-1 aptamer的丝素蛋白瘤内免疫水凝胶，通过系统的参数质控，优化最佳实验条件；以负载单抗的丝素蛋白水凝胶、裸药为对照，对我国常见消化道恶性肿瘤胃癌/结肠癌小鼠体内模型，研究其体内药物分布，对注射部位肿瘤及非注射部位肿瘤局部的免疫微环境调节作用，对全身免疫环境的调节作用，并系统评价局部给药后局部及全身的抗肿瘤效果，及对肿瘤二次暴露的预防作用；为我国潜在自主知识产权的靶向肿瘤免疫微环境的丝素蛋白水凝胶的研制及向临床应用的过渡提供实验依据。

Intratumoral immunization, which is a locoregional theray, has been reported to be effective to systemic tumor metastsis. This study aims to establish a local delivery hydrogel system targeting tumor immune microenvironment with silk fibroin which is safe and biocompatible as the drug carrier and DNA aptamer as the targeting drug. After preparing injectable silk fibroin hydrogel, CpG ODN, CTLA 4 aptamer, PD - 1 aptamer and the corresponding monoclonal antibody are loaded. Through quality control and specification system parameters, we optimize the.experimental conditions, study and optimize its drug release effect, and study local and systemic the antitumor efficacy on tumor mice model of gastric cancer. We characterize the CD8 + T cells, the number of CTLA 4 / PD - 1 single positive and double positive proportion of T cells, the proportion of Treg in the tumor microenvironment. Our study is a potential clinical application with independent intellectual property rights.