Comb-like dynamic antimicrobial peptides for serum-resistant intracellular protein delivery and antibacterial treatment

Open AccessCCS ChemistryRESEARCH ARTICLES21 Oct 2024Comb-like dynamic antimicrobial peptides for serum-resistant intracellular protein delivery and antibacterial treatment Wenhua Cheng, Kunyu Chen, Yunqing Gu, Fang Zhu, Yiyun Cheng and Jingjing Hu Wenhua Cheng , Kunyu Chen , Yunqing Gu , Fang Zhu , Yiyun Cheng and Jingjing Hu https://doi.org/10.31635/ccschem.024.202404917 SectionsSupplemental MaterialAboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Intracellular protein delivery has attracted increasing attentions in protein drugs, vaccines, and genome editing biotherapeutics. Polymeric carriers are promising candidates for protein delivery, but usually suffer from limitations such as poor serum resistance and degradability. Herein, we developed a type of comb-like dynamic antimicrobial peptides (CDAMPs) to address the issues by grafting antimicrobial peptides onto a polycatechol via dynamic covalent linkages. Benefiting from the amphipathic/cationic nature and comb-like structures, CDAMPs exhibited strong protein binding capability even in serum, and successfully delivered proteins inside cells. The dynamic linkages enable efficient protein release triggered by pH and reactive oxygen species. More importantly, CDAMPs showed greatly improved antibacterial activity compared to free AMPs, efficiently inhibited bacterial infection in two animal models, and alleviated infection-induced inflammation by delivering superoxide dismutase. The study provides a robust strategy to design protein delivering materials based on bioactive peptides, and the CDAMPs showed promising applications in the treatment of bacterial infections and concomitant symptoms by co-delivering protein therapeutics. Download figure Download PowerPoint Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentNot Yet AssignedSupporting Information Copyright & Permissions© 2024 Chinese Chemical Society Downloaded 0 times PDF downloadLoading ...