Yang Xiaoyue, Yi Zhongchao, Liang Ying, Tong Sheng
F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, United States.
New York Blood Center, New York, New York 10065, United States.
ACS Appl Mater Interfaces. 2024 Dec 11;16(49):67235-67245. doi: 10.1021/acsami.4c13821. Epub 2024 Nov 25.
Exosomes are cell-released nanovesicles that regulate intercellular communication by transporting a variety of bioactive molecules. They play a crucial role in various physiological and pathological processes, such as the immune response, tissue regeneration, aging, and tumor progression. There has been growing interest in controlling exosome production, which could offer valuable tools for unraveling complex cell communication networks and enabling novel therapeutic applications. Magnetic iron oxide nanoparticles (MNPs), one of the few nanomaterials approved for clinical use, have been shown to remotely modulate cellular activities such as cytoskeleton reorganization, ion channel activation, and cell polarization. In this study, we systematically investigate the effects of MNPs, acting as nanoscale force transducers, on exosome production in two distinct cell types with different responses to mechanical stimuli. Our findings reveal that magnetic force applied to intracellular MNPs induces vesicle relocation and promotes the formation of actin stress fibers. Gene expression analysis further shows that intracellular magnetic force upregulates genes related to exosome transport and secretion as well as other pathways linked to exosome biogenesis. Notably, these forces substantially enhance exosome production, particularly MNP-containing exosomes, which are accompanied by increased intercellular exchange of MNPs. In summary, our study offers valuable insights into MNP-driven exosome production and presents potential strategies for enhancing cell communication and modulating nanoparticle distribution in nanomedicine.
外泌体是细胞释放的纳米囊泡,通过运输多种生物活性分子来调节细胞间通讯。它们在各种生理和病理过程中发挥着关键作用,如免疫反应、组织再生、衰老和肿瘤进展。人们对控制外泌体产生的兴趣日益浓厚,这可能为揭示复杂的细胞通讯网络和实现新的治疗应用提供有价值的工具。磁性氧化铁纳米颗粒(MNPs)是少数被批准用于临床的纳米材料之一,已被证明能远程调节细胞活动,如细胞骨架重组、离子通道激活和细胞极化。在本研究中,我们系统地研究了作为纳米级力传感器的MNPs对两种对机械刺激有不同反应的不同细胞类型中外泌体产生的影响。我们的研究结果表明,施加于细胞内MNPs的磁力诱导囊泡重新定位并促进肌动蛋白应力纤维的形成。基因表达分析进一步表明,细胞内磁力上调了与外泌体运输和分泌相关的基因以及与外泌体生物发生相关的其他途径。值得注意的是,这些力显著增强了外泌体的产生,特别是含MNP的外泌体,同时伴随着MNPs细胞间交换的增加。总之,我们的研究为MNP驱动的外泌体产生提供了有价值的见解,并提出了增强细胞通讯和调节纳米医学中纳米颗粒分布的潜在策略。
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