Synthetic Mimics of Antimicrobial Peptides for the Targeted Therapy of Multidrug‐Resistant Bacterial Infection

Abstract

Antibacterial materials are highly demanded in treatment of bacterial infection, especially severe ones with multidrug-resistance. Herein, pH-responsive polypeptide, i.e., poly-L-lysine modified by 1-(propylthio)acetic acid-3-octylimidazolium and citraconic anhydride (PLL-POIM-CA), is synthesized by post-polymerization modification of poly-L-lysine (PLL) with 1-(propylthio)acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA). It is observed that PLL-POIM-CA is stable under normal physiological condition, while CA cleaves rapidly at weakly acidic environment like bacterial infectious sites. The hydrolyzed PLL-POIM-CA exhibits excellent broad-spectrum antibacterial activities against Gram-negative bacteria of Escherichia coli and Gram-positive bacteria of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). In particular, the minimum inhibitory concentration (MIC) against multidrug-resistant bacteria like MRSA is as low as 7.8 μg mL −1 . Moreover, PLL-POIM-CA exhibits good biocompatibility with mouse fibroblast cells (L929) in vitro and improved hemocompatibility with an HC 50 exceeding 5000 μg mL −1 . Therefore, PLL-POIM-CA displays an excellent bacteria versus cells selectivity (HC 50 /MIC) over 534, which is 53 times higher than natural antimicrobial peptide of indolicidin. It is further demonstrated in vivo that the antimicrobial polypeptide effectively accelerates MRSA-infected wound healing by relieving local inflammatory response. Therefore, this targeted antimicrobial polypeptide has broad application prospects for the treatment of multidrug-resistant bacterial infection.

Magnetic-controlled dandelion-like nanocatalytic swarm for targeted biofilm elimination

“…However, studies have shown that the other major problem of most antibacterial drugs was their poor permeability into bacterial biofilms. 35,36 Bacterial biofilm is a membrane formed by bacteria in the process of growth to adapt to the environment. 37 In order to test the ability of FSDMSsF NPs to eliminate bacterial biofilm, a biofilm removal experiment was designed (Fig.…”

Recent Advances in Peptides-Based Stimuli-Responsive Materials for Biomedical and Therapeutic Applications: A Review

“…Gong et al synthesized a pH-responsive polypeptide (PLL-POIM-CA), containing poly- l -lysine (PLL) enhanced by 1-(propylthio) acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA), which mimicked antimicrobial peptides . These polypeptides are helpful as a handy treatment for multi-drug-resistant bacterial infections.…”

Antibacterial Polymers Based on Poly(2-hydroxyethyl methacrylate) and Thiazolium Groups with Hydrolytically Labile Linkages Leading to Inactive and Low Cytotoxic Compounds

“…Typical antimicrobial polymers stand out for their chemical stability; however, in the last few years, self-degradable and biodegradable polymer systems are also needed to reduce not only antimicrobial pollution in the environment but also degradability in vivo minimizes side effects in the body after eradicating bacterial infection [ 22 , 23 , 24 ]. The biodegradability of the polymers can be achieved by the presence or incorporation of labile chemical linkages such as ester, amide and carbonate bonds.…”