title: Synthesis and Mechanism Insight of a Peptide-Grafted Hyperbranched Polymer Nanosheet with Weak Positive Charges but Excellent Intrinsically Antibacterial Efficacy.
abstract: Antimicrobial resistance is an increasingly problematic issue in the world and there is a present and urgent need to develop new antimicrobial therapies without drug resistance. Antibacterial polymers are less susceptible to drug resistance but they are prone to inducing serious side effects due to high positive charge. Herein we report a peptide-grafted hyperbranched polymer which can self-assemble into unusual nanosheets with highly effective intrinsically antibacterial activity but weak positive charges (+ 6.1 mV). The hyperbranched polymer was synthesized by sequential Michael addition-based thiol-ene and free radical mediated thiol-ene reactions, and followed by ring-opening polymerization of N-carboxyanhydrides (NCAs). The nanosheet structure was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) studies. Furthermore, a novel "wrapping and penetrating" antibacterial mechanism of the nanosheets was revealed by TEM and it is the key to significantly decrease the positive charges but have a very low minimum inhibitory concentration (MIC) of 16 μg mL(-1) against typical Gram-positive and Gram-negative bacteria. Overall, our synthetic strategy demonstrates a new insight for synthesizing antibacterial nanomaterials with weak positive charges. Moreover, the unique antibacterial mechanism of our nanosheets may be extended for designing next-generation antibacterial agents without drug resistance.
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , 301 Middle Yanchang Road, Shanghai 200072, China.|Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University , 4800 Caoan Road, Shanghai 201804, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University , 4800 Caoan Road, Shanghai 201804, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University , 4800 Caoan Road, Shanghai 201804, China.
authors.forename: Fangyingkai
authors.initials: F
authors.lastname: Wang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , 301 Middle Yanchang Road, Shanghai 200072, China.|Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University , 4800 Caoan Road, Shanghai 201804, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Du
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival; D002478:Cells, Cultured; D025802:Electric Capacitance; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D011108:Polymers