doi:10.16597/j.cnki.issn.1002-154x.2025.02.002
复合纳米粒子的制备及在抗感染治疗中的应用研究
刘杭
(bet体育365官网网站,南京 211189)
摘 要
为了治疗创面感染并促进创伤修复,作者设计并合成了硫辛酸(LA)修饰的抗菌活性肽LA-KLLK(LA-K)和细胞亲和肽LA-LIANAK(LA-L),通过紫外交联制备了cLA-KLLK(cLA-K)、cLA-LIANAK(cLA-L)纳米粒子,以及一种新型抗生素复合纳米粒子cLA-LIANAK-KLLK(cLA-L-K)。cLA-K和cLA-L-K均表现出优异的广谱抗菌活性,其中对耐甲氧西林葡萄球菌的最小抑菌浓度(MIC)仅为4μg·mL-1,4h内对细菌的杀灭效率高达97%,并且对细菌的生物膜同样具有优异的杀灭和抑制作用。其中4倍MIC的cLA-L-K对大肠杆菌形成的生物膜的抑制效果高达85.2%。此外,cLA-L-K具有良好的生物安全性,当其浓度低于256μg·mL-1,溶血率低于5%,并且低浓度cLA-L-K(8μg·mL-1)对人脐静脉内皮细胞(HUVEC细胞)的促迁移效果明显，促增殖效果高达148%。此外，动物实验结果显示，加入16μg·mL-1cLA-L-K的小鼠组的创伤修复效果最佳，表明其作为抗生素具有潜在的临床应用前景。本研究为开发新型的抗生素提供了一种新的思路。
关键词 硫辛酸 抗菌肽 纳米粒子 广谱抗菌活性 生物安全性 抗感染治疗
Preparation of Composite Nanoparticle and its Application in Anti-infective Therapy Research
LIU Hang
(School of Chemistry and Chemical Engineering,Southeast University,Nanjing 211189,China)
Abstract
To address traumatic infections and promote wound healing, lipoic acid(LA) modified peptides LA-KLLK(LA-K) with notable antimicrobial activity, and LA-LIANAK(LA-L) with exceptional cell affinity,was designed and synthesized in the study. cLA-KLLK(cLA-K), cLA-LIANAK(cLA-L) nanoparticles, and a new type of antibiotic cLA-LIANAK-KLLK(cLA-L-K) composite nanoparticles were successfully fabricated utilizing UV cross-linking technology. The cLA-K and cLA-L-K exhibited excellent broad-spectrum antibacterial efficacy,possessing a minimum inhibitory concentration(MIC) of 4μg· mL-1 against methicillin-resistant Staphylococcus aureus, and achieving 97% bacterial eradication within 4 hours. These antimicrobial nanoparticles also demonstrated efficacious antibiofilm activity, particularly cLA-L-K(4 MIC) presenting an 85.2% inhibition of Escherichia coli(E. coli) biofilm formation. Furthermore, cLA-L-K nanoparticles exhibited favorable biosafety. When the concentration of cLA-L-K is lower than 256μg·mL-1, the hemolysis rate is less than 5%. The promotion effect of cLA-L-K on human umbilical vein endothelial cells(HUVEC cells) migration is significant, and the promotion effect on proliferation reaches up to around 148%. Furthermore, the results of animal experiments showed that the mice in the group adding 16 ug· mL-1 of cLA-L-K had the best trauma repair effect, suggesting its potential clinical application as an antibiotic in pharmaceutical chemistry. The study provides a new idea for the development of novel antibiotics.
Keywords lipoic acid antimicrobial peptide nanoparticle broad-spectrum antimicrobial activity biosafety anti-infection treatment