Biomimetic extracellular vesicles derived from chimeric antigen receptor monocytes to treat glioblastoma: An efficient and safe intranasal drug delivery nanoplatform

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-06-09 DOI:10.1016/j.bioactmat.2025.05.032

Qihong Cheng , Minjie Wang , Zijie Zhou , Huitang Xia , Shaojie Yu , Jianglin Zheng , Kai Zhu , Xudong Li , Xuan Wang , Tao Xin , Xiaobing Jiang , Junjun Li

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引用次数: 0

Abstract

Background

Extracellular vesicles (EVs) have emerged as a promising pharmacotherapeutic modality for glioblastoma (GBM) drug delivery. However, the clinical translation of EVs remains restricted due to their low yield and demanding extraction steps. Therefore, extracellular vesicle mimetics (EVMs), as alternatives to EVs, have received much attention.

Results

Herein, inspired by the inherent GBM tropism of monocytes and the editable target recognition ability of chimeric antigen receptors (CARs), we present the synthesis and systemic evaluation of a doxorubicin (DOX)-loaded nanoplatform (termed CAR-EVMs@DOX) generated by loading DOX into EVMs derived from CAR-modified monocytes (CAR-EVMs) via a modified extrusion method. Due to insufficient GBM drug delivery efficacy and great systemic toxicity caused by the resistance of the blood−brain barrier (BBB), CAR-EVMs@DOX can be administered intranasally to bypass the BBB, resulting in dramatic GBM-targeted migration and accumulation in the GBM site. Moreover, compared with intravenous administration, intranasal delivery of CAR-EVMs@DOX increases tumor inhibition efficacy while protecting against DOX-induced cardiotoxicity.

Conclusions

The findings of our study demonstrate that the intranasal administration of the facile and well-designed nanoplatform CAR-EVMs@DOX is an advanced drug delivery tactic for GBM therapy, with the potential for future clinical translation.

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嵌合抗原受体单核细胞衍生的仿生细胞外囊泡治疗胶质母细胞瘤：一种高效安全的鼻内给药纳米平台

细胞外囊泡（ev）已成为胶质母细胞瘤（GBM）药物输送的一种有前景的药物治疗方式。然而，由于其低产量和苛刻的提取步骤，电动汽车的临床转化仍然受到限制。因此，细胞外囊泡模拟物（EVMs）作为ev的替代品受到了广泛的关注。在此，受单核细胞固有的GBM倾向和嵌合抗原受体（CARs）可编辑的靶标识别能力的启发，我们提出了一种负载阿霉素（DOX）的纳米平台（称为CAR-EVMs@DOX）的合成和系统评价，该平台通过改进的挤压法将DOX加载到car修饰单核细胞（CAR-EVMs）衍生的evm中。由于GBM药物递送效果不足，且血脑屏障（BBB）的抵抗引起了巨大的全身毒性，CAR-EVMs@DOX可以通过鼻内给药绕过血脑屏障，导致GBM在GBM部位的剧烈靶向迁移和积累。此外，与静脉给药相比，鼻内给药CAR-EVMs@DOX增加了肿瘤抑制效果，同时保护了dox诱导的心脏毒性。我们的研究结果表明，鼻腔给药简便且设计良好的纳米平台CAR-EVMs@DOX是GBM治疗的一种先进的药物传递策略，具有未来临床转化的潜力。

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

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.