Multicolored, Sonosensitizer-Optimized Organic Mechanoluminescent Nanoparticles for Functional Sono-Optogenetics.

Light enables precise visualization and control of cellular processes, but its utility in deep tissues is fundamentally limited by poor optical penetration, particularly in the deep brain. Ultrasound-triggered mechanoluminescence offers a noninvasive strategy for remote light delivery, yet existing organic systems remain monochromatic and low-intensity, largely due to an incomplete understanding of ultrasound-induced emission. Here, we report a multicolor mechanoluminescence platform that couples reactive oxygen species-responsive chemiluminescent donors with fluorescent acceptors via Förster resonance energy transfer, generating tunable emission from blue (461 nm) to red (592 nm). Systematic screening potentially reveals that electronic energy gap-dependent reactive oxygen species generation serves as a predictive design principle for high-performance mechanoluminescent materials. The emitted spectrum and intensity are sufficient to activate ChR2, eOPN3 and ChRmine, enabling in vitro neuromodulation under focused ultrasound. By integrating spatially precise ultrasound with programmable photon output, this platform establishes a noninvasive strategy for deep-tissue neuromodulation and provides a foundation for applications in bioimaging, gene editing, and precision therapeutics.