Han Hong, Ma Xiaotian, Deng Weiting, Zhang Junhang, Tang Songsong, Pak On Shun, Zhu Lailai, Criado-Hidalgo Ernesto, Gong Chen, Karshalev Emil, Yoo Jounghyun, You Ming, Liu Ann, Wang Canran, Shen Hao K, Patel Payal N, Hays Claire L, Gunnarson Peter J, Li Lei, Zhang Yang, Dabiri John O, Wang Lihong V, Shapiro Mikhail G, Wu Di, Zhou Qifa, Greer Julia R, Gao Wei
Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
Kavli Nanoscience Institute, California Institute of Technology, Pasadena, CA, USA.
Sci Robot. 2024 Dec 11;9(97):eadp3593. doi: 10.1126/scirobotics.adp3593.
Micro- and nanorobots excel in navigating the intricate and often inaccessible areas of the human body, offering immense potential for applications such as disease diagnosis, precision drug delivery, detoxification, and minimally invasive surgery. Despite their promise, practical deployment faces hurdles, including achieving stable propulsion in complex in vivo biological environments, real-time imaging and localization through deep tissue, and precise remote control for targeted therapy and ensuring high therapeutic efficacy. To overcome these obstacles, we introduce a hydrogel-based, imaging-guided, bioresorbable acoustic microrobot (BAM) designed to navigate the human body with high stability. Constructed using two-photon polymerization, a BAM comprises magnetic nanoparticles and therapeutic agents integrated into its hydrogel matrix for precision control and drug delivery. The microrobot features an optimized surface chemistry with a hydrophobic inner layer to substantially enhance microbubble retention in biofluids with multiday functionality and a hydrophilic outer layer to minimize aggregation and promote timely degradation. The dual-opening bubble-trapping cavity design enables a BAM to maintain consistent and efficient acoustic propulsion across a range of biological fluids. Under focused ultrasound stimulation, the entrapped microbubbles oscillate and enhance the contrast for real-time ultrasound imaging, facilitating precise tracking and control of BAM movement through wireless magnetic navigation. Moreover, the hydrolysis-driven biodegradability of BAMs ensures its safe dissolution after treatment, posing no risk of long-term residual harm. Thorough in vitro and in vivo experimental evidence demonstrates the promising capabilities of BAMs in biomedical applications. This approach shows promise for advancing minimally invasive medical interventions and targeted therapeutic delivery.
微型和纳米机器人在导航人体复杂且通常难以到达的区域方面表现出色，在疾病诊断、精准药物递送、解毒和微创手术等应用中具有巨大潜力。尽管它们前景广阔，但实际应用面临诸多障碍，包括在复杂的体内生物环境中实现稳定推进、通过深层组织进行实时成像和定位，以及为靶向治疗进行精确远程控制并确保高治疗效果。为克服这些障碍，我们引入了一种基于水凝胶、成像引导、可生物降解的声学微型机器人（BAM），其设计用于在人体中实现高稳定性导航。通过双光子聚合构建而成，BAM包含磁性纳米颗粒和整合到其水凝胶基质中的治疗剂，用于精确控制和药物递送。该微型机器人具有优化的表面化学性质，其内层疏水，可在生物流体中显著增强微泡保留，具备多日功能，外层亲水，可最大程度减少聚集并促进及时降解。双开口气泡捕获腔设计使BAM能够在一系列生物流体中保持一致且高效的声学推进。在聚焦超声刺激下，捕获的微泡振荡并增强实时超声成像的对比度，便于通过无线磁导航精确跟踪和控制BAM的运动。此外，BAM的水解驱动生物降解性确保其在治疗后安全溶解，不会带来长期残留危害的风险。全面的体外和体内实验证据证明了BAM在生物医学应用中的潜力。这种方法为推进微创医疗干预和靶向治疗递送展现出了前景。
