Abundo Maria Paulene, Tifrea Anna T, Buss Marjorie T, Barturen-Larrea Pierina, Jin Zhiyang, Malounda Dina, Shapiro Mikhail G
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA 91125.
Proc Natl Acad Sci U S A. 2025 May 20;122(20):e2423078122. doi: 10.1073/pnas.2423078122. Epub 2025 May 14.
Delivering biomedicines to specific sites of disease using remote-controlled devices is a long-standing vision in biomedical research. However, most existing externally triggered delivery systems are based on complex micromachines that are controlled with electromagnetic waves and require custom external instrumentation. Here, we present a drug delivery platform based on a simple protein-containing hydrogel that can be both imaged and triggered to release drugs at specific locations using widely available diagnostic ultrasound devices. This technology is based on the addition of air-filled protein nanostructures called gas vesicles (GVs) to hydrogel delivery vehicles. While intact, GVs sterically block the release of drug payloads and allow the vehicle to be imaged with ultrasound. An increase in ultrasound pressure causes the collapse of GVs within the delivery vehicles at the desired anatomical location, instantly creating percolation channels in the hydrogel, massively increasing diffusivity, and leading to rapid drug release. Unlike previous ultrasound-actuated delivery approaches, both the imaging and release are performed using a simple diagnostic ultrasound probe ubiquitously available in clinical settings. We implement this concept by quantifying ultrasound-controlled drug diffusion and release in vitro and demonstrating image-guided protein delivery in vivo in the gastrointestinal (GI) tract following oral administration. We further validate this technology by using it to deliver anti-inflammatory antibodies to effectively treat a rat model of colitis. Targeted acoustic percolation switches (TAPS) open a conduit for local, image-guided drug delivery with a simple formulation and commonplace ultrasound equipment.
利用遥控设备将生物药物输送到特定疾病部位是生物医学研究中长期以来的愿景。然而，大多数现有的外部触发式给药系统基于复杂的微机器，这些微机器由电磁波控制，并且需要定制的外部仪器。在此，我们展示了一种基于简单含蛋白质水凝胶的药物递送平台，该平台可以使用广泛可用的诊断超声设备在特定位置进行成像并触发药物释放。这项技术基于向水凝胶递送载体中添加称为气体囊泡（GVs）的充气蛋白质纳米结构。在完整状态下，GVs会在空间上阻止药物 payload 的释放，并允许载体用超声成像。超声压力的增加会导致递送载体内的GVs在所需的解剖位置坍塌，立即在水凝胶中形成渗滤通道，大幅增加扩散率，并导致药物快速释放。与以前的超声驱动给药方法不同，成像和释放均使用临床环境中普遍可用的简单诊断超声探头进行。我们通过在体外量化超声控制的药物扩散和释放，并在口服给药后在胃肠道（GI）中展示体内图像引导的蛋白质递送，来实现这一概念。我们通过使用该技术递送抗炎抗体以有效治疗大鼠结肠炎模型，进一步验证了这项技术。靶向声学渗滤开关（TAPS）通过简单的配方和普通的超声设备为局部、图像引导的药物递送开辟了一条途径。
