Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
Department of Light Chemical Engineering, Guangdong Polytechnic, No. 20, Lanshi 2th Road, Chancheng District, Foshan, Guangdong, Foshan, 528041, China.
Carbohydr Polym. 2020 Apr 15;234:115928. doi: 10.1016/j.carbpol.2020.115928. Epub 2020 Jan 30.
We developed a co-delivery system of nitric oxide (NO) and antibiotic for the antibiotic-resistant bacterial infection therapy. The NO could disperse the bacterial biofilms and convert the bacteria into an antibiotic-susceptible planktonic form. Using the chitosan-graft-poly(amidoamine) dendrimer (CS-PAMAM) as the co-delivery system, methicillin (MET) and NO were conjugated successively to form CS-PAMAM-MET/NONOate. The positive CS-PAMAM could efficiently capture the negatively charged bacteria and PAMAM provide abundant reaction points for high payloads of NO and MET. The CS-PAMAM-MET/NONOate displayed effective and combined antibacterial activity to the E. coli and S. aureus. Particularly, for the MET-resistant S. aureus (MRSA), the CS-PAMAM-MET/NONOate displayed the synergistic antibacterial activity. In vivo wound healing assays also confirmed that CS-PAMAM-MET/NONOate could heal the infection formed by MRSA and then accelerate the wound healing effectively. Moreover, CS-PAMAM-MET/NONOate showed no toxicity towards 3T3 cells in vitro and rats in vivo, providing a readily but high-efficient strategy to drug-resistant bacterial infection therapy.
我们开发了一种用于治疗抗生素耐药细菌感染的一氧化氮（NO）和抗生素的共递送系统。NO 可以分散细菌生物膜，并将细菌转化为对抗生素敏感的浮游形式。使用壳聚糖接枝聚（酰胺-胺）树枝状大分子（CS-PAMAM）作为共递送系统，将甲氧西林（MET）和 NO 依次缀合形成 CS-PAMAM-MET/NONOate。带正电的 CS-PAMAM 可以有效地捕获带负电荷的细菌，而 PAMAM 则为高载量的 NO 和 MET 提供了丰富的反应点。CS-PAMAM-MET/NONOate 对大肠杆菌和金黄色葡萄球菌显示出有效的协同抗菌活性。特别是对于耐甲氧西林金黄色葡萄球菌（MRSA），CS-PAMAM-MET/NONOate 显示出协同抗菌活性。体内伤口愈合实验也证实 CS-PAMAM-MET/NONOate 可以治愈由 MRSA 引起的感染，并有效地加速伤口愈合。此外，CS-PAMAM-MET/NONOate 在体外对 3T3 细胞和体内大鼠均没有毒性，为治疗耐药细菌感染提供了一种简便而高效的策略。
