Intracellular photoswitchable neuropharmacology driven by luminescence from upconverting nanoparticles.

Photoswitchable drugs are small-molecule optical probes that enable chromatically selective control of drug efficacy. Such light-driven neuropharmacology normally uses UV-visible light. Here we report that luminescence from a NaYF4:TmYb nanoparticle can be used for "remote control" of the configuration of an azobenzene-based quaternary ammonium photochrome called "AAQ". Normally the thermodynamically favored trans configuration of AAQ blocks voltage-gated potassium channels. Such activity is reduced by UV irradiation, due to the photochemical trans to cis isomerization generated by UV light. Since cis-AAQ absorbs more blue-green light, this wavelength range can be used to reverse the effects of UV light. We found that in place of such direct photostimulation, the blue luminescence from NaYF4:TmYb upconverting nanoparticles could drive AAQ activation inside living cells so as to enable bi-directional control of voltage-gated ion channels using UV and near-infrared light.