Biology subjects

Pyatnitskiy, I.

Publications and source records attributed to Pyatnitskiy, I..

3 recordsLinked to original sources

bioRxiv2025

Hydrogen-bonded organic framework nanotransducers enabled sono-optogenetics for Parkinsonian rats

Cell-type-specific activation of parvalbumin (PV)-expressing neurons in the external globus pallidus (GPe) through optogenetics has shown promise in facilitating long-lasting movement dysfunction recovery in mice with Parkinsons disease. However, its translational potential is hindered by adverse effects stemming from the invasive implantation of optical fibers into the brain. In this study, we have developed a non-invasive optogenetics approach, utilizing focused ultrasound-triggered mechanoluminescent nanotransducers to enable remote photon delivery deep in the brain for genetically targeted neuromodulation. These mechanoluminescent nanotransducers consist of sonosensitized hydrogen-bonded frameworks and chemiluminescent L012, serving as a nanoscale light source through ultrasound-induced cascade reactions. This system offers high ultrasound-triggered brightness and long-lasting light emission, facilitating repeatable deep brain stimulation. Our sono-optogenetics technology demonstrated effective modulation in the mouse motor cortex for limb motion control and activation of PV-GPe neurons for rescuing movement dysfunction over time in dopamine-depleted Parkinsons disease rats. This approach demonstrates the pathway for achieving genetically targeted and non-invasive neuromodulation for long-lasting treatment of Parkinsons disease, towards non-human primate models and clinical applications.

bioengineering↗

bioRxiv2024

Bioadhesive Hydrogel-Coupled and Miniaturized Ultrasound Transducer System for Long-Term, Wearable Neuromodulation

Transcranial focused ultrasound has become a promising non-invasive approach for neuromodulation applications, particularly for neurodegenerative diseases and psychiatric illnesses. However, its implementation in wearable neuromodulation has thus far been limited due to the devices large size, which needs external supporting systems for the neuromodulation process. Furthermore, the need for ultrasound gel for acoustic coupling between the device and skin limits the viability for long-term use, due to its inherent susceptibility to dehydration and lack of adhesiveness to form a stable interface. Here, we report a wearable miniaturized ultrasound device with size comparable to standard EEG/ECG electrodes integrated with bioadhesive hydrogel to achieve efficient acoustic intensity upon ultrasound stimulation for long-term, wearable primary somatosensory cortical stimulation. Specifically, air-cavity Fresnel lens (ACFAL) based self-focusing acoustic transducer (SFAT) was fabricated using a lithography-free microfabrication process. Our transducer was able to achieve an acoustic intensity of up to 30.7 W/cm2 (1.92 MPa) in free-field with a focal depth of 10 mm. Bioadhesive hydrogel was developed to address the need for long-term stability of acoustic couplant for ultrasound application. The hydrogel demonstrated less than 13% attenuation in acoustic intensity and stable adhesion force of 0.961 N/cm over 35 days. Leveraging our bioadhesive hydrogel-integrated wearable ultrasound transducer, we were able to suppress somatosensory evoked potentials elicited by median nerve stimulation via functional electrical stimulation over 28 days, demonstrating the efficacy of our transducer for long-term, wearable neuromodulation in the brain.

bioengineering↗

bioRxiv2023

Ultrasound programmable hydrogen-bonded organic frameworks for sono-chemogenetics

The precise control of mechanochemical activation within deep tissues via non-invasive ultrasound holds profound implications for advancing our understanding of fundamental biomedical sciences and revolutionizing disease treatments. However, a theory-guided mechanoresponsive materials system with well-defined ultrasound activation has yet to be explored. Here we present the concept of using porous hydrogen-bonded organic frameworks (HOFs) as toolkits for focused ultrasound programmably triggered drug activation to control specific cellular events in the deep brain, through on-demand scission of the supramolecular interactions. A theoretical model is developed to visualize the mechanochemical scission and ultrasound mechanics, providing valuable guidelines for the rational design of mechanoresponsive materials at the molecular level to achieve programmable and spatiotemporal activation control. To demonstrate the practicality of this approach, we encapsulate designer drug clozapine N-oxide (CNO) into the optimal HOF nanoparticles for FUS gated release to activate engineered G-protein-coupled receptors in the mice and rat ventral tegmental area (VTA), and hence achieved targeted neural circuits modulation even at depth 9 mm with a latency of seconds. This work demonstrates the capability of ultrasound to precisely control molecular interaction and develops ultrasound programmable HOFs to minimally invasive and spatiotemporally control cellular events, thereby facilitating the establishment of precise molecular therapeutic possibilities. We anticipate that this research could serve as a source of inspiration for precise and non-invasive molecular manipulation techniques, potentially applicable in programming molecular robots to achieve sophisticated control over cellular events in deep tissues.

bioengineering↗