RT Journal Article
SR Electronic
T1 Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial Infection
JF Antimicrobial Agents and Chemotherapy
JO Antimicrob. Agents Chemother.
FD American Society for Microbiology
SP e00368-18
DO 10.1128/AAC.00368-18
VO 62
IS 11
A1 Zhang, Rui
A1 Wu, Fengbo
A1 Wu, Lei
A1 Tian, Yaomei
A1 Zhou, Bailing
A1 Zhang, Xueyan
A1 Huang, Rong
A1 Yu, Chaoheng
A1 He, Gu
A1 Yang, Li
YR 2018
UL http://aac.asm.org/content/62/11/e00368-18.abstract
AB Owing to their broad-spectrum antibacterial properties, multitarget 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 hemolysis 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 (DP7) with cholesterol to form an amphiphilic conjugate. The prepared DP7-C easily self-assembled into stable nanomicelles in aqueous solution. The DP7-C micelles showed lower hemolytic activity than their unconjugated counterparts toward human red blood cells and a maximum tolerated dose of 80 mg/kg of body weight 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 models of infection. In conclusion, DP7-C micelles may be an excellent candidate for the treatment of bacterial infections in the clinic.