Li Zhengxing, Guo Zhongyuan, Zhang Fangyu, Sun Lei, Luan Hao, Fang Zheng, Dedrick Jeramy L, Zhang Yichen, Tang Christine, Zhu Audrey, Yu Yiyan, Ding Shichao, Wang Dan, Chang An-Yi, Yin Lu, Russell Lynn M, Gao Weiwei, Fang Ronnie H, Zhang Liangfang, Wang Joseph
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA.
Program in Materials Science and Engineering, University of California San Diego, La Jolla, CA, USA.
Nat Commun. 2025 Jan 14;16(1):666. doi: 10.1038/s41467-025-56032-4.
Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.
在呼吸系统疾病患病率不断上升的背景下，有效的肺部治疗方式的重要性比以往任何时候都更加关键。然而，当前的药物递送系统面临着重大限制，阻碍了它们的疗效和治疗效果。生物杂交微型机器人在体内主动药物递送方面显示出了巨大的潜力，特别是通过气管内途径用于肺部应用。然而，气管内给药的侵入性性质对其临床转化构成了障碍。在此，我们报告了一种将微型机器人高效无创吸入递送至肺部的方法。使用雾化器将微微型真核藻类微型机器人包裹在小的气溶胶颗粒中，使其能够到达下呼吸道。雾化后，微型机器人保持其运动性（约55μm/s），有助于实现肺部的均匀分布并在肺部长期留存超过五天。在耐甲氧西林金黄色葡萄球菌急性肺炎小鼠模型中，使用这种肺部吸入方法递送负载万古霉素的血小板膜包被聚合物纳米颗粒功能化的微型机器人，证明了治疗效果。这些有前景的发现强调了可吸入生物杂交微型机器人在无需麻醉的情况下的优势，突出了这种递送系统在常规临床应用中的巨大转化潜力。
