A Rigid Nanoplatform for Precise and Responsive Treatment of Intracellular Multidrug-Resistant Bacteria

作     者：Shaoqi Qu Xiaoyong Huang Xiangbin Song Yifan Wu Xiaowei Ma Jianzhong Shen Kui Zhu Shaoqi Qu;Xiaoyong Huang;Xiangbin Song;Yifan Wu;Xiaowei Ma;Jianzhong Shen;Kui Zhu

作者机构：National Center for Veterinary Drug Safety EvaluationCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100193China Guangdong Laboratory for Lingnan Modern Agricultur 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2022年第8卷第8期

页      面：57-66页

核心收录：

学科分类：0710[理学-生物学] 100208[医学-临床检验诊断学] 1002[医学-临床医学] 07[理学] 1001[医学-基础医学(可授医学、理学学位)] 070205[理学-凝聚态物理] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 0702[理学-物理学] 10[医学] 

基　　金：supported by the Laboratory of Lingnan Modern Agriculture Project(NT2021006) State Key Laboratory of Veterinary Biotechnology Foundation(SKLVBF202102)。 

主　　题：Antibiotic Bacteria Mesoporous silica Phospholipid Rigidity 

摘      要：Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host cells.Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications.Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular antibiotics.Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as models.In addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes.Finally,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia.These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.