Liu Hao, Zhang Xu, Zhao Ziyin, Yang Fangping, Xue Ruizhong, Yin Lichen, Song Ziyuan, Cheng Jianjun, Luan Shifang, Tang Haoyu
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China.
Biomater Sci. 2021 Apr 7;9(7):2721-2731. doi: 10.1039/d0bm02151b. Epub 2021 Feb 22.
Antimicrobial peptides (AMPs) have been considered as a promising new tool to combat the antimicrobial resistance (AMR) crisis. However, the high toxicity and high cost of AMPs hampered their further development. Herein, a series of star poly(-lysine) (PLL) homo- and copolymers with excellent antimicrobial activity and improved biocompatibility were prepared by the combination of ultra-fast ring opening polymerization (ROP) and side-chain modification. The amine-terminated polyamidoamine dendrimer (Gx-PAMAM) mediated ROP of Nε-tert-butyloxycarbonyl--lysine N-carboxyanhydride (Boc--Lys-NCA) and γ-benzyl--glutamic acid-based N-carboxyanhydride (PBLG-NCA) was able to prepare star PLL homo- and copolymers with 400 residues within 50 min. While the star PLL homopolymers exhibited low minimum inhibitory concentration (MIC = 50-200 μg mL) against both Gram-positive and Gram-negative bacteria (i.e., S. aureus and E. coli), they showed high toxicity against various mammalian cell lines. The star PLL copolymers with low contents of hydrophobic and hydroxyl groups showed enhanced antimicrobial activity (MIC = 25-50 μg mL) and improved mammalian cell viability. Both SEM and CLSM results indicated the antimicrobial mechanism of membrane disruption.
抗菌肽（AMPs）被认为是应对抗菌药物耐药性（AMR）危机的一种有前途的新工具。然而，AMPs的高毒性和高成本阻碍了它们的进一步发展。在此，通过超快速开环聚合（ROP）和侧链修饰相结合，制备了一系列具有优异抗菌活性和改善生物相容性的星形聚（赖氨酸）（PLL）均聚物和共聚物。胺端基聚酰胺胺树枝状大分子（Gx-PAMAM）介导的Nε-叔丁氧羰基-L-赖氨酸N-羧基酐（Boc-L-Lys-NCA）和γ-苄基-L-谷氨酸基N-羧基酐（PBLG-NCA）的ROP能够在50分钟内制备出含有400个残基的星形PLL均聚物和共聚物。虽然星形PLL均聚物对革兰氏阳性菌和革兰氏阴性菌（即金黄色葡萄球菌和大肠杆菌）均表现出较低的最低抑菌浓度（MIC = 50-200 μg/mL），但它们对各种哺乳动物细胞系显示出高毒性。具有低含量疏水基团和羟基的星形PLL共聚物表现出增强的抗菌活性（MIC = 25-50 μg/mL）和改善的哺乳动物细胞活力。扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）结果均表明其抗菌机制为膜破坏。
