Delivery of extracellular vesicles loaded with immune checkpoint inhibitors for immunotherapeutic management of glioma

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio Pub Date : 2024-09-14 DOI:10.1016/j.mtbio.2024.101244

Shang-Wen Lin, Cheng-Ping Yu, Jui-Chen Tsai, Yan-Jye Shyong

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Abstract

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro, as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma.

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细胞外囊泡装载免疫检查点抑制剂，用于胶质瘤的免疫治疗

胶质瘤是一种常见的原发性恶性脑肿瘤，存活率很低。使用免疫检查点抑制剂（ICI）进行免疫治疗是治疗胶质瘤的一种选择，而细胞外囊泡（EVs）因其增强的屏障渗透能力和免疫调节作用，被认为是一种潜在的药物输送系统，可用于各种疾病的治疗。本研究的目的是开发在治疗胶质瘤方面具有足够疗效的 ICI 负载 EVs（ICI/EV）。研究使用磷酸钙颗粒（CaP）刺激小鼠巨噬细胞分泌EVs。对细胞进行 CaP 调理后，EVs 分泌量增加，巨噬细胞极化为促炎表型。实验表明，CaP诱导的EV能在体外将巨噬细胞极化为促炎表型，这与调理方法有关。利用超声法成功制备了ICI/EVs，其负载效率很高。鼻内给药后，EVs 可分布于整个大脑，并有助于 ICIs 分布到胶质瘤病灶中。使用 ICI/EVs 对神经胶质瘤小鼠进行联合治疗可减少肿瘤体积，延长小鼠存活时间。在接受 ICI/EVs 治疗的小鼠中观察到细胞毒性 T 细胞浸润、肿瘤相关巨噬细胞极化和肿瘤增殖降低。所开发的 ICI/EVs 在神经胶质瘤的免疫治疗方面显示出前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Materials Today Bio Multiple-

CiteScore

8.30

自引率

4.90%

发文量

303

审稿时长

30 days

期刊介绍： Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).