Inhalable biohybrid microrobots: a non-invasive approach for lung treatment

• Published in: Nature communications 2025-01, Vol.16 (1), p.666-13, Article 666
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 13; 13/21; 13/31; 14; 14/34; 14/63; 147/135; 59; 59/5; 631/61/350; 631/61/54/152; 639/166/985; 639/301/54/152; Administration, Inhalation; Aerosols; Algae; Anesthesia; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Disease Models, Animal; Drug delivery; Drug delivery systems; Drug Delivery Systems - instrumentation; Drug resistance; Effectiveness; Female; Health services; Humanities and Social Sciences; Humans; In vivo methods and tests; Inhalation; Lung; Lung diseases; Lungs; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Microrobots; Motility; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Nebulizers and Vaporizers; Respiration; Respiratory diseases; Respiratory tract; Science; Science (multidisciplinary); Staphylococcal Infections - drug therapy; Staphylococcus infections; Trachea; Vancomycin; Vancomycin - administration & dosage
• ISSN: 2041-1723; 2041-1723
• 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 -1 ) 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. Reaching the depths of the respiratory tract is hard even with vapor-based drug delivery. Here, the authors devise inhalable biohybrid microrobots that, thanks to their motility, reach deeper regions of the lungs.