Antibiotic resistance has become one of the greatest health threats in the world. In this study, a charge-dispersed dimerization strategy is described for the antimicrobial peptide (AMP) mimics via a tunable cationic charge to improve the selectivity between prokaryotic microbes and eukaryotic cells. This strategy is demonstrated with a series of charge-dispersed AMP mimics based on N-arylimidazolium skeletons. These N-arylimidazolium AMP mimics show potent antibacterial activity against strains along with a low rate of drug resistance, good hemocompatibility, and low cytotoxicity. In addition to the elimination of planktonic bacteria, N-arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillinresistant Staphylococcus aureus (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of N-arylimidazolium AMP mimic, which enable the design of N-arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptidedecorated hyaluronic acid was synthesized, and the grafted Fmocphenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with β-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π−π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.

In traditional blood-contacting medical devices, infection and thrombosis are easily formed on the surface of the materials. In addition, inflammation is also a clinical complication that cannot be ignored. More importantly, there is a mutually promoting relationship between the inflammatory response and the infection as well as thrombosis. In this work, we propose a self-adaptive antiinflammatory coating strategy combined with anti-infection and anticoagulant capacity, which was accomplished based on nano-Ag particles and dexamethasone (Dex)-loaded hydrogel coating. The coating loaded with nano-Ag endows it with good bactericidal performance, including Gram-positive and Gram-negative bacteria. As an anti-inflammatory drug, Dex was grafted onto hydrogel coating by a reactive oxygen species (ROS)-cleavable thioketal (TK) bond and released upon the trigger of an inflammatory environment, blocking further inflammatory cascade, providing self-adaptive antiinflammatory properties, and avoiding side effects of the drug. It was demonstrated that the coating worked as a precise strategy to resist coagulation, infection, and inflammation, provided a new perspective for designing clinical complication-conformable coatings, and had great application prospects on blood-contacting medical devices.