ICAM-1-targeted and antibacterial peptide modified polymeric nanoparticles for specific combating sepsis. (October 2022)

• Record Type: Journal Article
• Authors: Pan, Lingling; Jiang, Dawei; Pan, Luqi; Meng, Zhizhen; Zhuang, Yangyang; Huang, Yueyue; Ye, Fanrong; Shi, Changcan; Chen, Jie; Pan, Jingye
• Is Part Of: Materials & design. Volume 222(2022)
• Publication Date: 2022-10
• Subjects: Sepsis -- Infection -- ICAM-1 -- Antimicrobial peptide -- Nanoparticles; Materials -- Periodicals; Engineering design -- Periodicals; Matériaux -- Périodiques; Conception technique -- Périodiques; Electronic journals; 620.11
• DOI: 10.1016/j.matdes.2022.111007
• Languages: English
• ISSNs: 0264-1275

Abstract

Graphic abstract: Inflammation targeting antibacterial peptides polymeric nanoparticles (anti-ICAM-1-AMPNP) were prepared for combating sepsis. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and biotin grafted PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization (ROP) and click chemistry. Antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly. The anti-ICAM-1-AMPNP nanoparticles could efficiently target the site of infection with upregulated expression of ICAM-1. Highlights: A strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. The anti-ICAM-1-AMPNP nanoparticles exhibited ideal antibacterial property. Inflammation response could be reduced obviously after treatment by anti-ICAM-1-AMPNP nanoparticles. Abstract: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and causes high ratios of morbidity and mortality worldwide. Although many potential therapeutic targets have been reported, the therapeutic effect needs to be further improved. Herein, we report a strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization and click chemistry. Then, antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly of amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 and PCL- b -P(OEGMA- co -AMA)- g -biotin in aqueous solution. Intercellular adhesion molecule-1 (ICAM-1) is highly expressed on the surface of inflammatory endothelial cells, and the anti-ICAM-1 antibody can specifically bind to it. To obtain the anti-ICAM-1-AMPNP nanoparticles, biotinylated anti-ICAM-1 antibodies were bonded on the surface of AMPNP nanoparticles through the biotin-avidin system. The anti-ICAM-1-AMPNP nanoparticles had low systemic toxicity and exhibited ideal antibacterial property against drug-resistant bacteria, Gram-negative bacteria and Gram-positive bacteria. The anti-ICAM-1-AMPNP nanoparticles exhibited favorable targeting capabilities to inflammation endothelial cells in vitro and significantly reduced the inflammatory response of CLP mice in vivo . The present investigation might provide a specific strategy for targeting combating sepsis with anti-ICAM-1-AMPNP nanoparticles.