Near-Infrared Manipulation of Membrane Ion Channels via Upconversion Optogenetics

Membrane ion channels are ultimately responsible for the propagation and integration of electrical signals in the nervous, muscular, and other systems. Their activation or malfunctioning plays a significant role in physiological and pathophysiological processes. Using optogenetics to dynamically and spatiotemporally control ion channels has recently attracted considerable attention. However, most of the established optogenetic tools (e.g., channelrhodopsins, ChRs) for optical manipulations, are mainly stimulated by UV or visible light, which raises the concerns of potential photodamage, limited tissue penetration, and high-invasive implantation of optical fiber devices. Near-infrared (NIR) upconversion nanoparticle (UCNP)-mediated optogenetic systems provide great opportunities for overcoming the problems encountered in the manipulation of ion channels in deep tissues. Hence, this review focuses on the recent advances in NIR regulation of membrane ion channels via upconversion optogenetics in biomedical research. The engineering and applications of upconversion optogenetic systems by the incorporation multiple emissive UCNPs into various light-gated ChRs/ligands are first elaborated, followed by a detailed discussion of the technical improvements for more precise and efficient control of membrane channels. Finally, the future perspectives for refining and advancing NIR-mediated upconversion optogenetics into in vivo even in clinical applications are proposed.