In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma.
In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma.
复制标题
DOI：
10.1016/j.jconrel.2022.03.050
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Xiaoqi Wang;Lu Ye;W. He;C. Teng;Shanbo Sun;Hongdan Lu;Shengnan Li;Lingyan Lv;Xiang Cao-Xiang-Ca
中科院分区：
文献类型：
--
作者：
Xiaoqi Wang;Lu Ye;W. He;C. Teng;Shanbo Sun;Hongdan Lu;Shengnan Li;Lingyan Lv;Xiang Cao-Xiang-Ca
众所周知，胶质瘤是目前恶性程度最高的脑肿瘤。由于血脑屏障（BBB）和肿瘤细胞异质性的存在，全身化疗对于手术切除后的胶质瘤的治疗效果并不理想，甚至可能损害机体的免疫系统。在这里，我们开发了一种原位缓释水凝胶递送系统，通过切除腔局部递送联合化疗药物和免疫佐剂，用于胶质瘤的化学免疫联合治疗。简而言之，将神经胶质瘤归巢肽修饰的紫杉醇靶向纳米颗粒（PNPPTX）和甘露醇化免疫佐剂CpG靶向纳米颗粒（MNPCpG）嵌入PLGA1750-PEG1500-PLGA1750热敏水凝胶框架（PNPPTX＆MNPCpG@Gel）中。体外和体内结果表明，当注射到胶质瘤切除腔中时，靶向纳米颗粒-水凝胶杂化系统可以交联成凝胶药物储库。然后，缓释的PNPPTX可以靶向残留的浸润胶质瘤细胞并产生肿瘤抗原。同时，MNPCpG靶向并激活抗原呈递细胞，增强肿瘤抗原呈递能力，激活CD8+T和NK细胞，逆转胶质瘤微环境的免疫抑制。本研究表明PNPPTX&MNPCpG@Gel系统可以增强化疗免疫疗法对胶质瘤的治疗效果。
It is well known that glioma is currently the most malignant brain tumor. Because of the existence of blood-brain barrier (BBB) and tumor cell heterogeneity, systemic chemotherapy exerts unsatisfied therapeutic effect for the treatment of glioma after surgical resection and may even damage the body's immune system. Here, we developed anin situsustained-release hydrogel delivery system for combined chemo-immunotherapy of glioma by combined chemotherapy drug and immunoadjuvant through the resection cavity local delivery. Briefly, glioma homing peptide modified paclitaxel targeting nanoparticles (PNPPTX) and mannitolated immunoadjuvant CpG targeting nanoparticles (MNPCpG) were embedded into PLGA1750-PEG1500-PLGA1750thermosensitive hydrogel framework (PNPPTX&MNPCpG@Gel). Thein vitroandin vivoresults showed that the targeting nanoparticles-hydrogel hybrid system could cross-link into a gel drug reservoir when injected into the resection cavity of glioma. And then, the sustained-release PNPPTXcould target the residual infiltration glioma cells and produce tumor antigens. Meanwhile, MNPCpGtargeted and activated the antigen-presenting cells, which enhanced the tumor antigen presentation ability and activated CD8+T and NK cells to reverse immunosuppression of glioma microenvironment. This study indicated that the PNPPTX&MNPCpG@Gel system could enhance the therapeutic effect of glioma by chemo-immunotherapy.