“…11 Despite these early advances, an important limitation of many current approaches is that invasive fiber or implanted micro light-emitting diodes are needed to activate photosensitive proteins for regulating activity of cells in deep tissue regions, which inevitably causes tissue damage, inflammation, infection, and limitations of animal behaviors. 12 Recently, lots of luminescent nanomaterials, such as lanthanide-doped upconversion nanoparticles (UCNPs), 13,14 scintillants, 15 quaternary oxysulfides, 16 graphene, 17 and liposomes, 18 have been broadly used as light transducers to activate photosensitive proteins through near-infrared light, Xray, or magnetic forces with deeper tissue penetration to realize noninvasive and tether-free optogenetic applications. 19,20 However, a major challenge remains that they provide little or even no control over the strength, timing, or cellular context of the therapeutic effect through a closed-loop regulation.…”