H-bonded organic frameworks as ultrasound-programmable delivery platform.
Wenliang Wang1, Yanshu Shi2, Wenrui Chai3
1Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Nature
|February 5, 2025
Summary
Researchers developed porous hydrogen-bonded organic frameworks (HOFs) for ultrasound-triggered drug release in deep tissues. This breakthrough enables precise control of cellular events for advanced disease treatments.
Area of Science:
- Biomedical Engineering
- Materials Science
- Neuroscience
Background:
- Precise control of mechanochemical activation in deep tissues via non-invasive ultrasound is crucial for biomedical science and disease treatment.
- A theory-guided mechanoresponsive material system with well-defined ultrasound activation is currently lacking.
Purpose of the Study:
- To introduce porous hydrogen-bonded organic frameworks (HOFs) as a toolkit for focused ultrasound (FUS)-programmably triggered drug activation.
- To control specific cellular events in the deep brain by on-demand scission of supramolecular interactions.
- To develop a theoretical model for visualizing mechanochemical scission and ultrasound mechanics to guide material design.
Main Methods:
- Utilized porous hydrogen-bonded organic frameworks (HOFs) as drug delivery vehicles.
- Encapsulated clozapine N-oxide (CNO) into HOF nanocrystals.
- Employed focused ultrasound (FUS) for triggered drug release.
- Activated engineered G-protein-coupled receptors in the ventral tegmental area (VTA) of mice and rats.
Main Results:
- Demonstrated FUS-gated drug release from HOFs.
- Achieved targeted neural circuit modulation in deep brain regions (9 mm depth) with a latency of seconds.
- Showcased the ability of ultrasound to precisely control molecular interactions.
Conclusions:
- Developed ultrasound-programmable HOFs for non-invasive, spatiotemporal control of cellular events.
- Established a novel approach for precise molecular therapeutics.
- Validated the potential of HOFs and FUS for deep-tissue biomedical applications.
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