美国得克萨斯大学奥斯汀分校Wang Huiliang团队报道了作为超声可编程传递平台的氢键有机框架。相关研究成果发表在2025年2月5日出版的国际知名学术期刊《自然》。

利用非侵入性超声在深层组织中实现机械化学激活的精准调控，对推动基础生物医学的理解和疾病治疗变革具有深远意义。然而，目前尚未有理论指导的、具有明确超声响应机制的材料体系被开发。

该文提出了一种利用多孔氢键有机框架（HOFs）作为聚焦超声（FUS）程序化触发药物激活工具的新策略，通过按需切断超分子相互作用实现对大脑深层特定细胞事件的调控。研究人员构建了一个可视化机械化学键断裂与超声力学过程的理论模型，为合理设计机械响应材料以实现程序化控制提供了重要指导。

为验证该方法的实用性，研究人员将设计药物氯氮平N-氧化物（CNO）封装于优化的HOF纳米晶中，通过FUS门控释放激活小鼠和大鼠腹侧被盖区（VTA）工程化G蛋白偶联受体，从而在9毫米深度实现秒级延迟的靶向神经回路调控。

该项工作不仅揭示了超声精确调控分子相互作用的潜力，更开发了超声可编程HOF材料，实现了对细胞事件的无创时空精准控制，为建立精准分子治疗新范式提供了可能。

附：英文原文

Title: H-bonded organic frameworks as ultrasound-programmable delivery platform

Author: 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

Issue&Volume: 2025-02-05

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 treatments1,2,3,4. However, a theory-guided mechanoresponsive materials system with well-defined ultrasound activation has yet to be explored5,6. 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 9mm 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.

DOI: 10.1038/s41586-024-08401-0

Source: https://www.nature.com/articles/s41586-024-08401-0