NIDA IRP Technology Resource Initiative Featured Paper

H-bonded organic frameworks as ultrasound-programmable delivery platform

Published in Nature.

Authors

Wenliang Wang, Yanshu Shi, Wenrui Chai, Kai Wing Kevin Tang, Ilya Pyatnitskiy, Yi Xie, Xiangping Liu, Weilong He, Jinmo Jeong, Ju-Chun Hsieh, Anakaren Romero Lozano, Brinkley Artman, Xi Shi, Nicole Hoefer, Binita Shrestha, Noah B Stern, Wei Zhou, David W McComb, Tyrone Porter, Graeme Henkelman, Banglin Chen, Huiliang Wang

Paper presented by Dr. Reinis Svarcbahs and selected by the NIDA TRI Paper of the Month Committee

Publication Brief Description

This study developed a focused ultrasound (FUS)-responsive hydrogen-bonded organic framework (HOF) nanoparticle platform for controlled drug delivery. The authors synthesized porous HOF nanocrystals with tunable hydrogen-bonding and π–π interactions, which can be dissociated by ultrasound stimulation to release the loaded cargo. As a proof-of-concept, the chemogenetic ligand clozapine-N-oxide (CNO) was loaded into the most ultrasound-sensitive HOF formulation. The results demonstrated that focused ultrasound could trigger drug release both in cultured neurons and in the brains of mice and rats, leading to activation of DREADD-expressing neurons in deep brain regions with a response latency of only a few seconds.

Wang, Wenliang; Shi, Yanshu; Chai, Wenrui; Tang, Kai Wing Kevin; Pyatnitskiy, Ilya; Xie, Yi; Liu, Xiangping; He, Weilong; Jeong, Jinmo; Hsieh, Ju-Chun; Lozano, Anakaren Romero; Artman, Brinkley; Shi, Xi; Hoefer, Nicole; Shrestha, Binita; Stern, Noah B; Zhou, Wei; McComb, David W; Porter, Tyrone; Henkelman, Graeme; Chen, Banglin; Wang, Huiliang

H-bonded organic frameworks as ultrasound-programmable delivery platform Journal Article

In: Nature, vol. 638, no. 8050, pp. 401–410, 2025, ISSN: 1476-4687.

Abstract | Links

@article{pmid39910310,

title = {H-bonded organic frameworks as ultrasound-programmable delivery platform},

author = {Wenliang Wang and Yanshu Shi and Wenrui Chai and Kai Wing Kevin Tang and Ilya Pyatnitskiy and Yi Xie and Xiangping Liu and Weilong He and Jinmo Jeong and Ju-Chun Hsieh and Anakaren Romero Lozano and Brinkley Artman and Xi Shi and Nicole Hoefer and Binita Shrestha and Noah B Stern and Wei Zhou and David W McComb and Tyrone Porter and Graeme Henkelman and Banglin Chen and Huiliang Wang},

url = {https://pubmed.ncbi.nlm.nih.gov/39910310/},

doi = {10.1038/s41586-024-08401-0},

issn = {1476-4687},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-01},

journal = {Nature},

volume = {638},

number = {8050},

pages = {401--410},

abstract = {The precise control of mechanochemical activation within deep tissues using 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 (FUS) 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 potentially visualize the mechanochemical scission and ultrasound mechanics, providing valuable guidelines for the rational design of mechanoresponsive materials to achieve programmable control. To demonstrate the practicality of this approach, we encapsulate the designer drug clozapine N-oxide (CNO) into the optimal HOF nanocrystals for FUS-gated release to activate engineered G-protein-coupled receptors in the ventral tegmental area (VTA) of mice and rats and hence achieve targeted neural circuit modulation even at depth 9 mm with a latency of seconds. This work demonstrates the capability of ultrasound to precisely control molecular interactions and develops ultrasound-programmable HOFs to non-invasively and spatiotemporally control cellular events, thereby facilitating the establishment of precise molecular therapeutic possibilities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}