Invasive brain implants and tethered optical fibres are typically used in restrained or motion-impaired animals, limiting the control and the decoding of the neural circuitry in freely behaving ones. Here we report the implant- and tether-free optical neurostimulation of deep brain regions by locally injected and untargeted photothermal transducers. The macromolecular transducers, comprising a semiconducting polymer core and an amphiphilic polymer shell, have an average diameter of 40 nanometres and achieve a photothermal conversion of 71% (at 1064 nm), activating the transient receptor potential cation channel subfamily V member 1 (TRPV1) ectopically expressed by an adeno-associated virus in dopaminergic neurons of tyrosine hydroxylase-driven Cre recombinase transgenic mice. The near-transparency of biological tissue in the second near-infrared window enabled the light source to be placed at 50 centimetres above the mouse, at a low incident power density of 10 milliwatt/square millimetre, resulting in the activation, through the scalp and skull, of the dopaminergic neurons in the ventral tegmental area, with minimal thermal damage. The approach is suitable for the neurostimulation of socially interacting mice.

Mechanoluminescent materials, which emit light in response to mechanical stimuli, have recently been explored as promising candidates for photonic skins, remote optogenetics, and stress sensing. All mechanoluminescent materials reported thus far are bulk solids with micron-sized grains, and their light emission is only produced when fractured or deformed in bulk form. In contrast, mechanoluminescence has never been observed in liquids and colloidal solutions, thus limiting its biological application in living organisms. Here, we report the synthesis of mechanoluminescent fluids via a suppressed dissolution approach. We demonstrate that this approach yields stable colloidal solutions comprising mechanoluminescent nanocrystals with bright emissions in the range of 470–610 nm and diameters down to 20 nm. These colloidal solutions can be recharged and discharged repeatedly under photoexcitation and hydrodynamically focused ultrasound, respectively, thus yielding rechargeable mechanoluminescent fluids that can store photon energy in a reversible manner. This rechargeable fluid can facilitate a systemically delivered light source gated by tissue-penetrant ultrasound for biological applications that require light in the tissue, such as optogenetic stimulation in the brain.

Many in vivo biological techniques, such as fluorescence imaging, photodynamic therapy, and optogenetics, require light delivery into biological tissues. The limited tissue penetration of visible light discourages the use of external light sources and calls for the development of light sources that can be delivered in vivo. A promising material for internal light delivery is persistent phosphors; however, there is a scarcity of materials with strong persistent luminescence of visible light in a stable colloid to facilitate systemic delivery in vivo. Here, we used a bioinspired demineralization (BID) strategy to synthesize stable colloidal solutions of solid-state phosphors in the range of 470 to 650 nm and diameters down to 20 nm. The exceptional brightness of BID-produced colloids enables their utility as multicolor luminescent tags in vivo with favorable biocompatibility. Because of their stable dispersion in water, BID-produced nanophosphors can be delivered systemically, acting as an intravascular colloidal light source to internally excite genetically encoded fluorescent reporters within the mouse brain.