Holographic focused ultrasound enables multitarget EV and MSC delivery for neurovascular repair after ischemic stroke

IF 18.1 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2026-10-25 DOI:10.1038/s41467-026-78847-5

Jia-Ji Pan, Chenyu Li, Xinya Yao, Yan Wei, Lan Shen, Xiangkun Piao, Mingyu Wang, Ji Hu, Guo-Yuan Yang, Yanbo Pei, Bingbing Cheng

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引用次数: 0

Abstract

Noninvasive multitarget delivery of size-diverse therapeutics, including extracellular vesicles (EVs) and mesenchymal stromal cells (MSCs), to peri-infarct zones is hindered by the blood-brain barrier (BBB) and heterogeneous infarct topographies. Here, we developed a hologram-assisted multitarget BBB opening (HaMBO) platform combining low-cost 3D-printed holograms with a single-element ultrasound transducer. Spatially tailored acoustic fields enabled localized BBB opening along infarct borders. In male mice with transient focal cerebral ischemia, a single two-minute HaMBO treatment safely enhanced the peri-infarct delivery of EVs and MSCs, reduced brain atrophy by ~56%, increased angiogenesis by ~2-fold and neural progenitor proliferation by ~4-fold, and improved long-term behavioral recovery. Spatial transcriptomic analysis associated HaMBO-assisted EV therapy with reduced macrophage infiltration and enhanced pro-angiogenic and neurogenic signaling. Human skull-based simulations further demonstrated HaMBO’s clinical adaptability across diverse stroke scenarios. Thus, HaMBO provides a safe, low-cost, and customizable platform for noninvasive multitarget delivery in ischemic stroke and other neurological disorders.

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全息聚焦超声可实现缺血性卒中后神经血管修复的多靶点EV和MSC输送

不同大小的治疗药物，包括细胞外囊泡（EVs）和间充质基质细胞（MSCs），非侵入性多靶点递送到梗死周围区域受到血脑屏障（BBB）和异质梗死地形的阻碍。在这里，我们开发了一个全息图辅助的多目标BBB打开（HaMBO）平台，将低成本的3d打印全息图与单元件超声换能器相结合。空间定制的声场使局部血脑屏障沿梗死边界开放。在短暂局灶性脑缺血的雄性小鼠中，单次2分钟的HaMBO治疗安全增强了梗死周围ev和MSCs的递送，减少了约56%的脑萎缩，增加了约2倍的血管生成和约4倍的神经祖细胞增殖，并改善了长期行为恢复。空间转录组学分析将hambo辅助的EV治疗与巨噬细胞浸润减少和促血管生成和神经生成信号增强联系起来。基于人类头骨的模拟进一步证明了HaMBO在不同中风情况下的临床适应性。因此，HaMBO为缺血性卒中和其他神经系统疾病的无创多靶点递送提供了一种安全、低成本和可定制的平台。

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

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.