Ultrasound (US) activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release. However, the typical US frequency used for mechanochemistry is around 20 kHz, producing inertial cavitation that exceeds the tolerance threshold of biological systems. Here, high-intensity focused US (HIFU) as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers (HBSPs) and microgels (MGLs). The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular cyclization. We reveal that HBSPs and MGLs effectively transduce HIFU as mechanical input to chemical output, demonstrated by the quantification of the release of fluorescent umbelliferone (UMB). Moreover, an in vitro study of drug release is carried out using camptothecin as the model drug, which is covalently loaded in MGLs, demonstrating the potential of our system for controlled drug delivery to cancer cells.

超声波（US）激活聚合物中的力力团，引发级联化学反应，是按需分子释放的一种有前途的策略。然而，美国用于机械化学的典型频率约为 20 kHz，产生的惯性空化超过了生物系统的耐受阈值。在这里，引入高强度聚焦超声（HIFU）作为机械刺激来驱动超支化星形聚合物（HBSP）和微凝胶（MGL）中二硫键机械团的激活。分子释放的机制归因于硫醇-二硫化物交换反应和随后的分子内环化。我们揭示了 HBSP 和 MGL 有效地将 HIFU 作为机械输入转变成化学输出，这通过荧光伞形酮 (UMB) 释放的量化得到证明。此外，使用喜树碱作为模型药物进行了药物释放的体外研究，喜树碱共价负载在 MGL 中，证明了我们的系统控制药物递送至癌细胞的潜力。