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Experimental Therapeutics

Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial Infection

Rui Zhang, Fengbo Wu, Lei Wu, Yaomei Tian, Bailing Zhou, Xueyan Zhang, Rong Huang, Chaoheng Yu, Gu He, Li Yang
Rui Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Fengbo Wu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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  • ORCID record for Fengbo Wu
Lei Wu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Yaomei Tian
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Bailing Zhou
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Xueyan Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Rong Huang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Chaoheng Yu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Gu He
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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Li Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, ChinaCollaborative Innovation Center, Chengdu, Sichuan, China
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DOI: 10.1128/AAC.00368-18
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ABSTRACT

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.

FOOTNOTES

    • Received 23 February 2018.
    • Returned for modification 27 March 2018.
    • Accepted 27 August 2018.
    • Accepted manuscript posted online 10 September 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00368-18.

  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

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Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial Infection
Rui Zhang, Fengbo Wu, Lei Wu, Yaomei Tian, Bailing Zhou, Xueyan Zhang, Rong Huang, Chaoheng Yu, Gu He, Li Yang
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00368-18; DOI: 10.1128/AAC.00368-18

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Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial Infection
Rui Zhang, Fengbo Wu, Lei Wu, Yaomei Tian, Bailing Zhou, Xueyan Zhang, Rong Huang, Chaoheng Yu, Gu He, Li Yang
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00368-18; DOI: 10.1128/AAC.00368-18
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KEYWORDS

antimicrobial peptide
micelle
hemolytic effect
immune regulation
systemic administration

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