Influence of cationic groups on the antibacterial behavior of cationic nano-sized hyperbranched polymers to enhance bacteria-infected wound healing.

With the continuous emergence of drug-resistant pathogens, new strategies with high antibacterial efficacy are urgently needed. Herein, five cationic nano-sized hyperbranched polymers (CNHBPs) with cationic functional groups have been constructed, and their antibacterial mechanism has been studied in detail. CNHBPs bearing secondary ammonium salt groups and long alkyl chains (S12-CNHBP) exhibited weak antibacterial and antibiofilm ability, while CNHBPs bearing quaternary ammonium salt groups and long alkyl chains (Q12-CNHBP) showed the highest antimicrobial and strongest antibiofilm activities. ζ potential and isothermal titration microcalorimetry (ITC) results suggest that the negatively charged surfaces of bacterial cells provided Q12-CNHBP with a higher intrinsic electrostatic driving force for bacterial killing than that with S12-CNHBP. Fluorescent tracing and morphological observations indicate that the bacterial genome might be another antibacterial target for S12-CNHBP in addition to the cell wall and membrane, which are mainly antibacterial targets for Q12-CNHBP, making it less likely to induce bacterial resistance. Surprisingly, Q12-CNHBP exhibited superior in vivo therapeutic efficacy in a mouse wound model of methicillin-resistant Staphylococcus aureus (MRSA) infection with low toxicity during treatment. These advantages and ease of preparation will undoubtedly distinguish Q12-CNHBP as a new class of suitable candidates to combat multidrug-resistant pathogen infections. This study opens up a new avenue for exploiting antibacterial biomaterials to treat infections caused by drug-resistant bacteria.

Secondary Ammonium-Based Hyperbranched Poly(amidoamine) with Excellent Membrane-Active Property for Multidrug-Resistant Bacterial Infection.

With the rapid emergence of microbial infections induced by "superbugs", public health and the global economy are threatened by the lack of effective and biocompatible antibacterial agents. Herein, we systematically design a series of secondary ammonium-based hyperbranched poly(amidoamine) (SAHBP) with different alkyl chain lengths for probing high-efficacy antibacterial agents. SAHBP modified with alkyl tails at the hyperbranched core could efficiently kill Escherichia coli and Staphylococcus aureus, two types of clinically important bacteria worldwide. The best SAHBP with 12-carbon-long alkyl tails (SAHBP-12) also showed high activity against problematic multidrug-resistant bacteria, including Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). Based on ζ potential, isothermal titration microcalorimetry (ITC), and membrane integrity assays, it is found that SAHBP-12 could attach to the cell membrane via electrostatic adsorption and hydrophobic interactions, following which the integrity of the bacterial cell wall and the cell membrane is disrupted, resulting in severe cell membrane damage and the leakage of cytoplasmic contents, finally causing bacterial cell death. Impressively, benefiting from excellent membrane-active property, SAHBP-12 exhibited robust therapeutic efficacy in MRSA-infected mice wounds. Moreover, SAHBP-12 also showed excellent biosafety in vitro and in vivo, which undoubtedly distinguished it as a potent weapon in combating the growing threat of problematic multidrug-resistant bacterial infections.