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

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

机构地区：[1]College of Veterinary Medicine,Northeast Agricultural University,Harbin 150030,China [2]Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development,Harbin 150030,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第3期160-176,共17页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.3210190403);the Natural Science Foundation of Heilongjiang Province(No.YQ2022C016);the China Postdoctoral Science Foundation(2022T150104and 2020M670877);the Postdoctoral Science Foundation of Heilongjiang Province(LBH-TZ2104 and LBH-Z20039);the China Agriculture Research System of MOF and MARA(No.CARS-35)。

摘　　要：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-G2loaded 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~2log 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.

关 键 词：MRSA biofilm ISOLIQUIRITIGENIN Dimer prodrug Charge adaptive Responsive nanoparticles 

分 类 号：R943[医药卫生—药剂学]