| Summary: | Abstract Stimulating ion channels targeting in neuromodulation by external signals with the help of functionalized nanoparticles, which integrates the pioneering achievements in the fields of neurosciences and nanomaterials, has involved into a novel interdisciplinary field. The emerging technique developed in this field enable simple, remote, non-invasive, and spatiotemporally precise nerve regulations and disease therapeutics, beyond traditional treatment methods. In this paper, we define this emerging field as nano-neuromodulation and summarize the most recent developments of non-genetic nano-neuromodulation (non-genetic NNM) over the past decade based on the innovative design concepts of neuromodulation nanoparticle systems. These nanosystems, which feature diverse compositions, structures and synthesis approaches, could absorb certain exogenous stimuli like light, sound, electric or magnetic signals, and subsequently mediate mutual transformations between above signals, or chemical reactions, to regulate stimuli-sensitive ion channels and ion migrations which play vital roles in the nervous system. We will also discuss the obstacles and challenges in the future development of non-genetic NNM, and propose its future developments, to add the further progress of this promising field. Graphical Abstract
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