Lung- specific supramolecular nanoparticles for efficient delivery of therapeutic proteins and genome editing nucleases

• 成果类型: Article
• 署名作者: Liu, Ji; Zheng, Qizhen; Yao, Rui; Wang, Ming
• 署名单位: Chinese Academy of Sciences; Institute of Chemistry, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12801
• DOI: 10.1073/pnas.2406654121
• 发表日期: 2024-08-13
• 关键词: hydrogen-peroxide; messenger-rna

摘要

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 Lung- Specific Supramolecular Nanoparticles (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.