Infection-responsive polysaccharide-based drug-loaded nano-assembly for dual-modal treatment against drug-resistant bacterial lung infection  

作　　者：Lin Han Zhonghua Yuan Hui-Min Ren Weizhuo Song Ruonan Wu Jie Li Zhaoyan Guo Bingran Yu Shun Duan Fu-Jian Xu 

机构地区：[1]State Key Laboratory of Chemical Resource Engineering,Key Lab of Biomedical Materials of Natural Macromolecules(Beijing University of Chemical Technology,Ministry of Education),Beijing Laboratory of Biomedical Materials,Beijing University of Chemical Technology,Beijing,China [2]Beijing Research Institute of Chemical Industry,Sinopec,Beijing,China

出　　处：《BMEMat(BioMedical Engineering Materials)》2024年第3期123-136,共14页生物医学工程材料（英文）

基　　金：Beijing Outstanding Young Scientist Program,Grant/Award Number:BJJWZYJH01201910010024;National Natural Science Foundation of China,Grant/Award Numbers:52073024,52122304,52221006,52293382;Beijing Municipal Science and Technology Project,Grant/Award Number:Z191100006619099。

摘　　要：The escalating issue of lung infections induced by multi-drug resistant(MDR)bacteria is threatening human health.Thus,the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively.Herein,we designed inhalable drug-loaded nano-assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer,quaternized polyethyleneimine(QPEI-C_(6)),as well as a kind of typical antibiotic for therapy of lung infection,azithromycin(AZT).By adjusting the feed ratios,we optimized the size of the nano-assembly to approximately 200 nm(STQ_(12)),which was beneficial for penetration through the mucus layer and biofilm.In the slightly acidic environment of the infected site,the nano-assembly could dissemble responsively and release AZT and QPEI-C_(6).Because of the combined bactericidal effect,STQ_(12)exhibited high bactericidal efficiency against MDR bacteria.In animal experiments,STQ_(12)showed notable efficacy against MDR bacterial lung infection.Gene transcriptomic results showed that the main effects of STQ_(12)against bacteria were through influencing the bacterial cell components and metabolic processes,and affecting their growth and reproduction.This work provides a promising strategy to treat MDR bacterium-induced lower respiratory tract infections.

关 键 词：ANTIBACTERIAL infection responsiveness multi-drug resistant bacteria NANO-ASSEMBLY POLYSACCHARIDE 

分 类 号：R318[医药卫生—生物医学工程] TB383[医药卫生—基础医学]