Acoustic hydrogen delivery to treat PANoptosis induced by myocardial ischemia/reperfusion injury in rats

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications Pub Date : 2026-06-01 Epub Date: 2026-02-09 DOI:10.1016/j.bioadv.2026.214770

Shu-Hui Wang , Chen-Hui Li , Zi-Jun Wei , Cai-Yun Tang , Yong Wang , Fei Yan , Qian Li

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引用次数: 0

Abstract

Myocardial ischemia/reperfusion (MIR) injury remains a major clinical challenge with limited therapeutic options. Although molecular hydrogen (H₂) possesses therapeutic potential, its clinical translation is hindered by poor solubility and the lack of targeted delivery and real-time monitoring capabilities. To address this, we developed hydrogen-loaded lipid microbubbles (H₂-MBs) for ultrasound-triggered, spatially controlled H₂ delivery. The fabricated H₂-MBs exhibited uniform spherical morphology (0.92 ± 0.03 μm), high concentration ((1.14 ± 0.07) × 10¹⁰ bubbles/mL), and efficient H₂ encapsulation, enabling real-time contrast-enhanced ultrasound imaging. In a rat model of MIR injury, intravenous injection of H₂-MBs followed by ultrasound-targeted microbubble destruction (UTMD) significantly improved cardiac function (ejection fraction and fractional shortening), reduced infarct size, and attenuated tissue damage. Mechanistic studies revealed that ultrasound-targeted H₂ release suppressed H₂O₂-induced PANoptosis—a synergistic cell death pathway—by concurrently downregulating key mediators of pyroptosis (cleaved caspase-1, GSDMD), apoptosis (cleaved caspase-3/8, Bax/Bcl-2 ratio), and necroptosis (p-RIPK1, p-RIPK3, p-MLKL). Our work presents a robust theranostic microsystem for image-guided, spatiotemporally controlled gas delivery, offering a promising strategy to combat MIR injury through coordinated modulation of inflammatory programmed cell death.

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声学氢输送治疗大鼠心肌缺血再灌注损伤所致PANoptosis。

心肌缺血/再灌注（MIR）损伤仍然是一个主要的临床挑战，治疗方案有限。虽然分子氢（H₂）具有治疗潜力，但其溶解性差、缺乏靶向递送和实时监测能力阻碍了其临床转化。为了解决这个问题，我们开发了载氢脂质微泡（H₂- mb），用于超声波触发，空间控制的H₂递送。制备的H₂- mb具有均匀的球形形貌（0.92±0.03 μm），高浓度（（1.14±0.07）× 1010个气泡/mL）和高效的H₂封装，可实现实时超声成像。在MIR损伤大鼠模型中，静脉注射H₂- mb后，超声靶向微泡破坏（UTMD）可显著改善心功能（射血分数和分数缩短），缩小梗死面积，减轻组织损伤。机制研究表明，超声靶向的H₂释放通过同时下调焦亡（cleaved caspase-1， GSDMD）、凋亡（cleaved caspase-3/8， Bax/Bcl-2比例）和坏死（p-RIPK1, p-RIPK3, p-MLKL）的关键介质，抑制H₂O₂诱导的panoptosis -一种协同细胞死亡途径。我们的工作提出了一个强大的治疗微系统，用于图像引导，时空控制的气体输送，提供了一个有前途的策略，通过协调调节炎症程序性细胞死亡来对抗MIR损伤。

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 Science & Engineering C-Materials for Biological Applications 工程技术-材料科学：生物材料

CiteScore

17.80

自引率

0.00%

发文量

501

审稿时长

27 days

期刊介绍： Biomaterials Advances, previously known as Materials Science and Engineering: C-Materials for Biological Applications (P-ISSN: 0928-4931, E-ISSN: 1873-0191). Includes topics at the interface of the biomedical sciences and materials engineering. These topics include: • Bioinspired and biomimetic materials for medical applications • Materials of biological origin for medical applications • Materials for "active" medical applications • Self-assembling and self-healing materials for medical applications • "Smart" (i.e., stimulus-response) materials for medical applications • Ceramic, metallic, polymeric, and composite materials for medical applications • Materials for in vivo sensing • Materials for in vivo imaging • Materials for delivery of pharmacologic agents and vaccines • Novel approaches for characterizing and modeling materials for medical applications Manuscripts on biological topics without a materials science component, or manuscripts on materials science without biological applications, will not be considered for publication in Materials Science and Engineering C. New submissions are first assessed for language, scope and originality (plagiarism check) and can be desk rejected before review if they need English language improvements, are out of scope or present excessive duplication with published sources. Biomaterials Advances sits within Elsevier''s biomaterials science portfolio alongside Biomaterials, Materials Today Bio and Biomaterials and Biosystems. As part of the broader Materials Today family, Biomaterials Advances offers authors rigorous peer review, rapid decisions, and high visibility. We look forward to receiving your submissions!