题目：

Inhaled immunoantimicrobials for the treatment of chronic obstructive pulmonary disease

作者：

Junliang Zhu^1#, Xiaohui Li^2#, Yang Zhou¹, Chenglong Ge¹, Xudong Li¹, Mengying Hou¹, Yuansong Wei¹, Yongbing Chen², Kam W. Leong³, Lichen Yin^1,2*

单位：

¹Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.

²Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215002, China.

³Department of Biomedical Engineering, Columbia University, New York, NY, USA.

摘要：

Effective therapeutic modalities and drug administration strategies for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations are lacking. Here, mucus and biofilm dual-penetrating immunoantimicrobials (IMAMs) are developed for bridging antibacterial therapy and pro-resolving immunotherapy of COPD. IMAMs are constructed from ceftazidime (CAZ)–encapsulated hollow mesoporous silica nanoparticles (HMSNs) gated with a charge/conformation-transformable polypeptide. The polypeptide adopts a negatively charged, random-coiled conformation, masking the pores of HMSNs to prevent antibiotic leakage and allowing the nebulized IMAMs to efficiently penetrate the bronchial mucus and biofilm. Inside the acidic biofilm, the polypeptide transforms into a cationic and rigid α helix, enhancing biofilm retention and unmasking the pores to release CAZ. Meanwhile, the polypeptide is conditionally activated to disrupt bacterial membranes and scavenge bacterial DNA, functioning as an adjuvant of CAZ to eradicate lung-colonizing bacteria and inhibiting Toll-like receptor 9 activation to foster inflammation resolution. This immunoantibacterial strategy may shift the current paradigm of COPD management.

影响因子：

14.957

分区情况：

一区

链接：

https://www.science.org/doi/10.1126/sciadv.abd7904