Novel self-assembled micelles based on cholesterol-modified antimicrobial peptide (DP7) for safe and effective systemic administration in bacteria-infected animal models [Experimental Therapeutics]

Owing to their broad-spectrum antibacterial properties, multi-target effects and low drug resistance, antimicrobial peptides (AMPs) have played critical roles in the clinical therapy of drug-resistant bacterial infections. However, the potential hazard of haemolysis following systemic administration has greatly limited their application. Here, we developed a novel AMP derivative, DP7-C, by modifying a formerly identified highly active AMP with cholesterol to form an amphiphilic conjugate. The prepared DP7-C easily self-assembled into stable nanomicelles in aqueous solution. Compared to unconjugated counterparts, the DP7-C micelles showed lower haemolytic activity toward human red blood cells and a maximum tolerated dose of 80 mg/kg in mice via intravenous injection, thus demonstrating improved safety. Moreover, by eliciting specific immunomodulatory activities in immune cells, the DP7-C micelles exerted distinct therapeutic effects in zebrafish and mouse infectious models. In conclusion, DP7-C micelles may be an excellent candidate for treatment of bacterial infections in the clinic.

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