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基因编辑 T 细胞膜包被的 AIEgen 纳米颗粒有效预防胶质母细胞瘤复发

英文原题:Genetically edited T-cell membrane coated AIEgen nanoparticles effectively prevents glioblastoma recurrence.

PubMed 2022/12/22(内容时间) Biomaterials Q1 · IF 13.6(JCR 2025)

研究概要

胶质母细胞瘤干细胞(GSCs)是导致胶质母细胞瘤(GBM)发生和复发的肿瘤起始细胞亚群。

中文摘要

胶质母细胞瘤干细胞(GSCs)是导致胶质母细胞瘤(GBM)发生和复发的肿瘤起始细胞亚群。由于血管内皮和GSCs具有不同的病理特征,同时抑制二者仍是一项挑战。在此,我们提出一种联合的全方位控制策略以实现局部光热治疗(PTT)。我们通过将基因工程T细胞膜(CM)包覆于聚集诱导发光(AIE)纳米颗粒上,设计了具有AIE特性的T细胞模拟纳米颗粒(CM@AIE NPs)。CM外壳被设计为靶向CD133和表皮生长因子受体(EGFR),这为同时靶向GBM细胞和GSCs进行肿瘤治疗提供了可能。CM@AIE NPs可作为紧密连接(TJ)调节剂触发细胞内信号级联反应,导致TJ破坏和肌动蛋白细胞骨架重排,使CM@AIE NPs能够静默穿越血脑屏障(BBB)。980 nm激发触发的PTT可完全抑制肿瘤发生和复发。CM包覆纳米技术与基因编辑技术的结合可启发进一步开发协同技术以预防GBM复发。

展开英文摘要原文

Glioblastoma stem cells (GSCs) are subpopulations of tumor-initiating cells responsible for glioblastoma (GBM) tumorigenesis and recurrence. Dual inhibition of vascular endothelium and GSCs is still a challenge due to their different pathological features. Here we present a combined all-in-control strategy to realize a local photothermal therapy (PTT). We designed T-cell-mimic nanoparticles with aggregation-induced emission (AIE) characteristics by coating the genetically engineered T cell membrane (CM) onto AIE nanoparticles (CM@AIE NPs). The CM shell was designed against CD133 and epidermal growth factor receptor (EGFR) which provides the possibility to target both GBM cells and GSCs for cancer therapy. CM@AIE NPs can serve as the tight junction (TJ) modulators to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to allow CM@AIE NPs to cross the blood-brain barrier (BBB) silently. The 980 nm excitation-triggered PTT can completely inhibit tumorigenesis and recurrence. The combination of CM-coating nanotechnology and genetic editing technique can inspire further development of synergetic techniques for preventing GBM recurrence.

论文信息

作者
Wang W、Wu F、Mohammadniaei M、Zhang M、Li Y、Sun Y、Tang BZ
第一作者单位
Department of Health Technology, Technical University of Denmark, Kongens Lyngby, DK-2800, Denmark.Denmark
通讯作者单位
School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China. Electronic address: tangbenz@cuhk.edu.cn.China
期刊
Biomaterials2023 Feb
原文标识
PubMed 36580721 · DOI 10.1016/j.biomaterials.2022.121981