Neuromodulation technologies such as deep brain stimulation and optogenetics have transformed the treatment of neurological disorders by enabling targeted control of dysfunctional neural circuits, yet their clinical adoption is limited by invasive surgical requirements, off-target effects, poor penetration depth, and lack of cell-type specificity. Current non-invasive methods like transcranial magnetic stimulation and transcranial direct current stimulation provide insufficient spatial precision and cannot effectively reach deep brain structures. Meanwhile, nanoparticle-based or liposomal light delivery approaches have struggled with stability, photon yield, and tissue penetration. With neurodegenerative diseases such as Parkinson’s disease on the rise, there is a critical need for a non-invasive, programmable neuromodulation approach capable of safely and selectively activating deep brain neural populations without the risks and costs associated with surgical interventions.
This technology introduces a non-invasive sono-optogenetic platform that uses hydrogen-bonded organic framework nanoparticles loaded with the chemiluminescent molecule L012 to achieve deep brain neural activation. When exposed to focused ultrasound, the nanoparticles generate singlet oxygen that reacts with L012 to emit approximately 470 nm blue light, enabling remote activation of channelrhodopsin-2 expressed in genetically targeted neurons. The system provides cell-type-specific stimulation with sub-4 millisecond latency, tunable pulse frequencies, and sustained light emission, achieving precise neural modulation without optical fibers or implanted devices. Demonstrated in vitro and in vivo, the platform has successfully modulated deep brain regions and restored motor function in Parkinsonian animal models. The nanoparticles’ high porosity and stability support efficient L012 loading and robust responsiveness to ultrasound, while biosafety evaluations show minimal toxicity and no significant neuroinflammatory response.
Addresses a major therapeutic gap by eliminating the need for invasive neuromodulation surgery Supports development of next-generation, non-invasive CNS therapeutics and diagnostic tools Strong potential for integration with ultrasound neuromodulation devices and clinical imaging systems Available for exclusive licensing
U.S. Provisional application serial no. 63/606,481 filed on 12/05/2023; PCT application serial no. PCT/US2024/058476 filed on 12/04/2024, published as WO 2025/122626