首页|Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection.However,their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity.Herein,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin(ISL)loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug(ISL-G2)bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized oligochitosan.The obtained ISL-G2 loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr)binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs.The NPs maintained their negatively charged surface,thus prolonging the blood circulation time.In response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the biofilms.Sequentially,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA.An in vivo study was performed on a MRSA biofilm infected wound model.This phytochemical-based system led to～2 log CFU(＞99％)reduction of biofilm MRSA as compared to untreated wound(P＜0.001)with negligible biotoxicity in mice.This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

MRSA biofilmIsoliquiritigeninDimer prodrugCharge adaptiveResponsive nanoparticles

Xilong Cui、Fanhui Liu、Shuang Cai、Tingting Wang、Sidi Zheng、Xinshu Zou、Linlin Wang、Siqi He、Yanhua Li、Zhiyun Zhang

展开 >

College of Veterinary Medicine,Northeast Agricultural University,Harbin 150030,China

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development,Harbin 150030,China

National Natural Science Foundation of ChinaNatural Science Foundation of Heilongjiang ProvinceChina Postdoctoral Science FoundationChina Postdoctoral Science FoundationPostdoctoral Science Foundation of Heilongjiang ProvincePostdoctoral Science Foundation of Heilongjiang ProvinceChina Agriculture Research System of MOF and MARAfoundation of Northeast Agricultural University

3210190403YQ2022C0162022T1501042020M670877LBH-TZ2104LBH-Z20039CARS-35

2024

10.1016/j.ajps.2024.100923

亚洲药物制剂科学(英文版)
沈阳药科大学

亚洲药物制剂科学(英文版)

ISSN：1818-0876
年,卷(期)：2024.19(3)