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

Zhengxing Li, Zhongyuan Guo, Fangyu Zhang, Lei Sun, Hao Luan, Zheng Fang, Jeramy L. Dedrick, Yichen Zhang, Christine Tang, Audrey Zhu, Yiyan Yu, Shichao Ding, Dan Wang, An-Yi Chang, Lu Yin, Lynn M. Russell, Weiwei Gao, Ronnie H. Fang, Liangfang Zhang () and Joseph Wang ()
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Zhengxing Li: University of California San Diego
Zhongyuan Guo: University of California San Diego
Fangyu Zhang: University of California San Diego
Lei Sun: University of California San Diego
Hao Luan: University of California San Diego
Zheng Fang: University of California San Diego
Jeramy L. Dedrick: University of California San Diego
Yichen Zhang: University of California San Diego
Christine Tang: University of California San Diego
Audrey Zhu: University of California San Diego
Yiyan Yu: University of California San Diego
Shichao Ding: University of California San Diego
Dan Wang: University of California San Diego
An-Yi Chang: University of California San Diego
Lu Yin: University of California San Diego
Lynn M. Russell: University of California San Diego
Weiwei Gao: University of California San Diego
Ronnie H. Fang: University of California San Diego
Liangfang Zhang: University of California San Diego
Joseph Wang: University of California San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-56032-4

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