化疗是脑胶质瘤术后治疗至关重要的一环。然而，全身系统化疗难以克服血脑屏障，而且破坏机体免疫系统，加剧胶质瘤微环境免疫抑制。通过胶质瘤手术腔内局部化疗联合免疫佐剂，不仅使化疗药物直达病灶，又可逆转胶质瘤免疫抑制，增强胶质瘤治疗效果。本项目将胶质瘤归巢肽修饰的紫杉醇靶向纳米粒（PTX-NPs）和甘露醇修饰的免疫佐剂CpG靶向纳米粒（CpG-NPs），嵌入PLGA-PEG-PLGA温敏凝胶三维骨架中，构建胶质瘤手术腔内化疗/免疫协同治疗的原位缓释凝胶递药系统。该系统以液体形式注射于胶质瘤术后空腔，在体温刺激下交联成凝胶药物储库，缓慢释放PTX-NPs靶向杀死胶质瘤细胞并产生肿瘤抗原；释放CpG-NPs靶向激活抗原提呈细胞，提高肿瘤抗原提呈能力，激活CD8+T和NK细胞，逆转胶质瘤免疫抑制，协同提高胶质瘤治疗效果。本项目为胶质瘤术后局部化疗联合免疫治疗研究提供了新思路，具有重要科学价值和临床前景。

Chemotherapy is a vital part of the treatment of glioblastoma after surgical resection. However, systemic chemotherapy is difficult to overcome the blood-brain barrier and damage the body's immune system which led to aggravate the immunosuppression microenvironment of glioma. Combined therapy of chemotherapy drug and immunoadjuvant through the resection cavity local delivery, which not only make the drug reach the lesion directly, but also reverse the immunosuppression of glioma and enhance the therapeutic effect of glioma. In this project, glioma homing peptide modified paclitaxel targeting nanoparticles (PTX-NPs) and mannitol modified immunoadjuvant CpG targeting nanoparticles (CpG-NPs) were embedded in PLGA-PEG-PLGA thermosensitive gel three-dimensional framework. In this study, an in situ sustained-release gel delivery system for synergistic chemotherapy/immunotherapy of glioma was constructed. The system is injected into the glioma resection cavity in liquid form, which will cross-linked into a gel drug reservoir under body temperature stimulation. The slowly released PTX-NPs will kill glioma cells and produce tumor antigens. The released CpG-NPs form the gel will target and activate the antigen-presenting cells, which improve the tumor antigen presentation ability and activating CD8+T and NK cells to reverse immunosuppression of glioma. The strategy will synergistically enhance the therapeutic effect of glioma. This project provides a new idea for the development of chemotherapy combined with immunotherapy for glioma after surgical resection, which has important scientific value and clinical prospects.