Affiliation:
1. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
2. University of Chinese Academy of Sciences, Beijing 100049, China
Abstract
Protein therapeutics play a critical role in treating a large variety of diseases, ranging from infections to genetic disorders. However, their delivery to target tissues beyond the liver, such as the lungs, remains a great challenge. Here, we report a universally applicable strategy for lung-targeted protein delivery by engineering
L
ung-Specific
S
upramolecular
N
ano
p
articles (LSNPs). These nanoparticles are designed through the hierarchical self-assembly of metal-organic polyhedra (MOP), featuring a customized surface chemistry that enables protein encapsulation and specific lung affinity after intravenous administration. Our design of LSNPs not only addresses the hurdles of cell membrane impermeability of protein and nonspecific tissue distribution of protein delivery, but also shows exceptional versatility in delivering various proteins, including those vital for anti-inflammatory and CRISPR-based genome editing to the lung, and across multiple animal species, including mice, rabbits, and dogs. Notably, the delivery of antimicrobial proteins using LSNPs effectively alleviates acute bacterial pneumonia, demonstrating a significant therapeutic potential. Our strategy not only surmounts the obstacles of tissue-specific protein delivery but also paves the way for targeted treatments in genetic disorders and combating antibiotic resistance, offering a versatile solution for precision protein therapy.
Funder
MOST | National Natural Science Foundation of China
北京市科学技术委员会 | Natural Science Foundation of Beijing Municipality
Publisher
Proceedings of the National Academy of Sciences