title: Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection.
abstract: We reported an erythrocyte membrane-coated nanogel (RBC-nanogel) system with combinatorial antivirulence and responsive antibiotic delivery for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. RBC membrane was coated onto the nanogel via a membrane vesicle templated in situ gelation process, whereas the redox-responsiveness was achieved by using a disulfide bond-based crosslinker. We demonstrated that the RBC-nanogels effectively neutralized MRSA-associated toxins in extracellular environment and the toxin neutralization in turn promoted bacterial uptake by macrophages. In intracellular reducing environment, the RBC-nanogels showed an accelerated drug release profile, which resulted in more effective bacterial inhibition. When added to the macrophages infected with intracellular MRSA bacteria, the RBC-nanogels significantly inhibited bacterial growth compared to free antibiotics and non-responsive nanogel counterparts. These results indicate the great potential of the RBC-nanogel system as a new and effective antimicrobial agent against MRSA infection.
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, China.
authors.forename: Wansong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Pavimol
authors.initials: P
authors.lastname: Angsantikul
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Spiekermann
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ronnie H
authors.initials: RH
authors.lastname: Fang
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Nanoengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: zhang@ucsd.edu.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000737:chemistry; D065546:Drug Liberation; D004910:Erythrocyte Membrane; D005782:Gels; D006460:Hemolysin Proteins / Q000737:chemistry; D008264:Macrophages / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005782:Gels; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D014640:Vancomycin
keywords: Antibiotic delivery; Cell membrane coating; Detoxification; Nanomedicine; Staph infection