纳米颗粒介导的离子通道操纵：从其膜相互作用到生物应用

离子通道是跨膜蛋白在所有控制各种离子（例如Na，K，Ca2和Cl-等）中遍布细胞质膜的细胞中的跨膜蛋白，它们在生理过程中起关键作用，包括调节信号转导，细胞增殖以及兴奋性细胞兴奋和传导。异常离子通道功能通常与功能障碍和许多疾病有关，例如神经退行性疾病，眼科疾病，肺部疾病甚至癌症。离子通道的精确调节不仅有助于破译生理和病理过程，而且还有望成为疾病治疗的尖端手段。最近，纳米颗粒介导的离子通道操纵是一种高度有希望的方法，可以满足其简单，高效，精确，时空控制和非侵入性调节的生物医学和其他研究边界的不创调节。 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离子通道等）。到目前为止，纳米颗粒介导的离子通道调节在神经和心血管调节，生理功能再生以及肿瘤治疗等的界面上显示了许多生物医学领域的潜在前景。在如此重要的领域中，在这篇典型的评论中，我们专门概述了不同类型的离子渠道及其与疾病有关的活动的最新研究。此外，将系统地总结不同类型的刺激响应纳米颗粒，它们的相互作用模式和针对质膜离子通道的策略。更重要的是，将讨论由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性发育相关的生物应用。最后但并非最不重要的一点是，该领域的当前挑战和未来观点也将被涵盖。

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.