Immunostimulant In Situ Fibrin Gel for Post-operative Glioblastoma Treatment by Macrophage Reprogramming and Photo–Chemo-Immunotherapy,ACS Applied Materials & Interfaces

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Immunostimulant In Situ Fibrin Gel for Post-operative Glioblastoma Treatment by Macrophage Reprogramming and Photo–Chemo-Immunotherapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-03-31 , DOI: 10.1021/acsami.3c00468
Ruotian Zhang _{1,

2,

3} , Yicheng Ye ₂ , Jianing Wu ₃ , Junbin Gao ₂ , Weichang Huang ₂ , Hanfeng Qin ₂ , Hao Tian ₂ , Mingyang Han ₃ , Boyan Zhao ₃ , Zhenying Sun ₃ , Xin Chen ₁ , Xingli Dong ₃ , Kun Liu ₂ , Chang Liu ₄ , Yingfeng Tu ₂ , Shiguang Zhao _{1,

3}

Affiliation

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.

中文翻译：

用于通过巨噬细胞重编程和光化学免疫疗法治疗术后胶质母细胞瘤的免疫刺激原位纤维蛋白凝胶

肿瘤复发仍然是胶质母细胞瘤 (GBM) 手术切除后治疗失败的主要原因。M2 样肿瘤相关巨噬细胞 (TAM) 浸润肿瘤组织促进肿瘤进展并严重损害化学疗法和免疫疗法的疗效。此外，设计能够穿过血脑屏障并引发适用的有机反应的药物是一项雄心勃勃的挑战。在这里，我们提出了一种可注射的纳米颗粒-水凝胶系统，该系统使用包裹在 M1 巨噬细胞衍生的纳米囊泡 (M1NV) 中的载有多柔比星 (DOX) 的介孔聚多巴胺 (MPDA) 纳米颗粒作为效应器，并使用纤维蛋白水凝胶作为原位运载工具。体内荧光成像显示，水凝胶系统在递送至次全 GBM 切除模型的瘤腔时会触发光化学免疫疗法以破坏剩余的肿瘤细胞。同时，流式细胞术的结果表明，M1NVs 通过将 M2 样 TAM 重编程为 M1 样 TAM，全面改善了免疫微环境。该水凝胶系统结合近红外激光有效促进T细胞持续浸润，恢复T细胞效应功能，抑制髓源性抑制细胞和调节性T细胞浸润，从而表现出强烈的抗肿瘤免疫反应，显着抑制肿瘤生长。因此，MPDA-DOX-NVs@Gel (MD-NVs@Gel) 为治疗 GBM 复发提供了一种独特的临床策略。同时，流式细胞术的结果表明，M1NVs 通过将 M2 样 TAM 重编程为 M1 样 TAM，全面改善了免疫微环境。该水凝胶系统结合近红外激光有效促进T细胞持续浸润，恢复T细胞效应功能，抑制髓源性抑制细胞和调节性T细胞浸润，从而表现出强烈的抗肿瘤免疫反应，显着抑制肿瘤生长。因此，MPDA-DOX-NVs@Gel (MD-NVs@Gel) 为治疗 GBM 复发提供了一种独特的临床策略。同时，流式细胞术的结果表明，M1NVs 通过将 M2 样 TAM 重编程为 M1 样 TAM，全面改善了免疫微环境。该水凝胶系统结合近红外激光有效促进T细胞持续浸润，恢复T细胞效应功能，抑制髓源性抑制细胞和调节性T细胞浸润，从而表现出强烈的抗肿瘤免疫反应，显着抑制肿瘤生长。因此，MPDA-DOX-NVs@Gel (MD-NVs@Gel) 为治疗 GBM 复发提供了一种独特的临床策略。该水凝胶系统结合近红外激光有效促进T细胞持续浸润，恢复T细胞效应功能，抑制髓源性抑制细胞和调节性T细胞浸润，从而表现出强烈的抗肿瘤免疫反应，显着抑制肿瘤生长。因此，MPDA-DOX-NVs@Gel (MD-NVs@Gel) 为治疗 GBM 复发提供了一种独特的临床策略。该水凝胶系统结合近红外激光有效促进T细胞持续浸润，恢复T细胞效应功能，抑制髓源性抑制细胞和调节性T细胞浸润，从而表现出强烈的抗肿瘤免疫反应，显着抑制肿瘤生长。因此，MPDA-DOX-NVs@Gel (MD-NVs@Gel) 为治疗 GBM 复发提供了一种独特的临床策略。

更新日期：2023-03-31

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