免疫疗法
肿瘤微环境
癌症研究
重编程
免疫系统
渗透(HVAC)
材料科学
流式细胞术
自愈水凝胶
光动力疗法
纤维蛋白
医学
细胞
免疫学
生物
化学
肿瘤细胞
遗传学
有机化学
高分子化学
复合材料
作者
Ruotian Zhang,Yicheng Ye,Jianing Wu,Junbin Gao,Wei-Chang Huang,Hanfeng Qin,Hao Tian,Mingyang Han,Boyan Zhao,Zhenying Sun,Xin Chen,Xinxin Dong,Kun Liu,Chang Liu,Yingfeng Tu,Shiguang Zhao
标识
DOI:10.1021/acsami.3c00468
摘要
Tumor recurrence remains the leading cause of treatment failure following surgical resection of glioblastoma (GBM). M2-like tumor-associated macrophages (TAMs) infiltrating the tumor tissue promote tumor progression and seriously impair the efficacy of chemotherapy and immunotherapy. In addition, designing drugs capable of crossing the blood-brain barrier and eliciting the applicable organic response is an ambitious challenge. Here, we propose an injectable nanoparticle-hydrogel system that uses doxorubicin (DOX)-loaded mesoporous polydopamine (MPDA) nanoparticles encapsulated in M1 macrophage-derived nanovesicles (M1NVs) as effectors and fibrin hydrogels as in situ delivery vehicles. In vivo fluorescence imaging shows that the hydrogel system triggers photo-chemo-immunotherapy to destroy remaining tumor cells when delivered to the tumor cavity of a model of subtotal GBM resection. Concomitantly, the result of flow cytometry indicated that M1NVs comprehensively improved the immune microenvironment by reprogramming M2-like TAMs to M1-like TAMs. This hydrogel system combined with a near-infrared laser effectively promoted the continuous infiltration of T cells, restored T cell effector function, inhibited the infiltration of myeloid-derived suppressor cells and regulatory T cells, and thereby exhibited a strong antitumor immune response and significantly inhibited tumor growth. Hence, MPDA-DOX-NVs@Gel (MD-NVs@Gel) presents a unique clinical strategy for the treatment of GBM recurrence.
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