Fenton Reaction-Mediated Endolysosomal Disruption for Efficient Cytosolic Protein Delivery

IF 16 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2025-09-25 DOI:10.1021/acsnano.5c01922

Peng Zhang, , , Qi Yao, , , Xiaonong Zhang, , , Xuan Yi*, , , Chunsheng Xiao*, , and , Xuesi Chen,

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Abstract

Endolysosomal entrapment is still the major obstacle in cytosolic protein delivery. Methods that can efficiently promote endolysosomal escape are thus highly demanded. Herein, the possibility of transferring proteins from endolysosomes into the cytosol by Fenton reaction-mediated endolysosomal disruption was examined. Proteins and iron ions were loaded in calcium carbonate nanoparticles, and the intracellular distribution and bioactivities of proteins after cellular uptake were analyzed. This technology, termed chemodynamic internalization (CDI), was found to efficiently deliver various proteins, including ribonuclease A, green fluorescent protein, β-galactosidase, and horseradish peroxidase, into the cytosol by mitochondrial calcium overload-enhanced Fenton reaction-mediated lipid peroxidation and ensuing rupture of endolysosomal membranes, maintaining the bioactivity of delivered proteins. Therefore, CDI provides an efficient and general tool for cytosolic protein delivery and may advance protein-related basic research and drug development.

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芬顿反应介导的内溶酶体破坏对有效的细胞质蛋白递送。

内溶酶体包裹仍然是胞质蛋白递送的主要障碍。因此，迫切需要能够有效促进内溶酶体逃逸的方法。本文研究了通过芬顿反应介导的内溶酶体破坏将蛋白从内溶酶体转移到细胞质中的可能性。将蛋白质和铁离子装入碳酸钙纳米颗粒中，分析蛋白质在细胞摄取后的细胞内分布和生物活性。这项技术被称为化学动力学内化（CDI），研究发现，通过线粒体钙超载增强的芬顿反应介导的脂质过氧化和随后的内溶酶体膜破裂，可以有效地将各种蛋白质（包括核糖核酸酶A、绿色荧光蛋白、β-半乳糖苷酶和辣根过氧化物酶）递送到细胞质中，保持所递送蛋白质的生物活性。因此，CDI为细胞内蛋白质传递提供了一种高效、通用的工具，并可能推动蛋白质相关的基础研究和药物开发。

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

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.