离子通道是跨膜蛋白，在所有细胞中普遍表达，控制各种离子（如Na+、K+、Ca2+和Cl-等）穿过细胞质膜，发挥调节信号转导、细胞增殖以及兴奋性细胞兴奋和传导等生理过程的关键作用。异常的离子通道功能通常与许多疾病相关，如神经退行性疾病、眼科疾病、肺部疾病甚至癌症。对离子通道的精确调节不仅有助于解密生理和病理过程，还有望成为疾病治疗的前沿手段。最近，纳米颗粒介导的离子通道调制成为一种极具潜力的方式，以满足生物医学研究和其他前沿领域对于简单、高效、精确、时空可控和非侵入性调节的日益增长的需求。由于其独特的物理性质，纳米颗粒不仅可以通过其微小尺寸效应直接阻塞离子通道的孔道位点或动力学，通过其带电表面扰动活动电压门控离子通道，还可以作为天线传导或增强外部物理刺激，以实现各种离子通道活动的时空、精确和高效调节（如光、机械和温度门控离子通道等）。到目前为止，纳米颗粒介导的离子通道调节已在神经调节、心血管调节、生理功能再生和肿瘤治疗等许多生物医学领域显示出潜在前景。在这篇典型综述中，我们特别概述了不同类型的离子通道及其与疾病相关的活动的最新研究。此外，我们将系统总结不同类型的刺激响应性纳米颗粒，它们与质膜离子通道的相互作用模式和靶向策略。更重要的是，将讨论功能性纳米颗粒介导的离子通道调节方法及其与生理调节和治疗开发相关的生物应用。最后但并非最不重要的是，我们还将涵盖当前挑战和未来前景。版权所有©2023 Elsevier B.V.。

Ion channels are transmembrane proteins ubiquitously expressed in all cells that control various ions (e.g. Na+, K+, Ca2+ and Cl- etc) crossing cellular plasma membrane, which play critical roles in physiological processes including regulating signal transduction, cell proliferation as well as excitatory cell excitation and conduction. Abnormal ion channel function is usually associated with dysfunctions and many diseases, such as neurodegenerative disorders, ophthalmic diseases, pulmonary diseases and even cancers. The precise regulation of ion channels not only helps to decipher physiological and pathological processes, but also is expected to become cutting-edge means for disease treatment. Recently, nanoparticles-mediated ion channel manipulation emerges as a highly promising way to meet the increasing requirements with respect to their simple, efficient, precise, spatiotemporally controllable and non-invasive regulation in biomedicine and other research frontiers. Thanks the advantages of their unique properties, nanoparticles can not only directly block the pore sites or kinetics of ion channels through their tiny size effect, and perturb active voltage-gated ion channel by their charged surface, but they can also act as antennas to conduct or enhance external physical stimuli to achieve spatiotemporal, precise and efficient regulation of various ion channel activities (e.g. light-, mechanical-, and temperature-gated ion channels etc). So far, nanoparticles-mediated ion channel regulation has shown potential prospects in many biomedical fields at the interfaces of neuro- and cardiovascular modulation, physiological function regeneration and tumor therapy et al. Towards such important fields, in this typical review, we specifically outline the latest studies of different types of ion channels and their activities relevant to the diseases. In addition, the different types of stimulation responsive nanoparticles, their interaction modes and targeting strategies towards the plasma membrane ion channels will be systematically summarized. More importantly, the ion channel regulatory methods mediated by functional nanoparticles and their bioapplications associated with physiological modulation and therapeutic development will be discussed. Last but not least, current challenges and future perspectives in this field will be covered as well.Copyright © 2023 Elsevier B.V. All rights reserved.