title: Bacteria-Activated Theranostic Nanoprobes against Methicillin-Resistant Staphylococcus aureus Infection.
abstract: Despite numerous advanced imaging and sterilization techniques available nowadays, the sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections remain big challenges. Here we report a strategy to design activatable theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) infections. This probe is based on silica nanoparticles coated with vancomycin-modified polyelectrolyte-cypate complexes (SiO2-Cy-Van), which is activated by an interesting phenomenon of bacteria-responsive dissociation of the polyelectrolyte from silica nanoparticles. Due to the aggregation of hydrophobic cypate fluorophores on silica nanoparticles to induce ground-state quenching, the SiO2-Cy-Van nanoprobes are nonfluorescent in aqueous environments. We demonstrate that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-cypate complexes from silica nanoparticles and draw them onto their own surface, changing the state of cypate from off (aggregation) to on (disaggregation) and leading to in vitro MRSA-activated near-infrared fluorescence (NIRF) and photothermal elimination involving bacterial cell wall and membrane disruption. In vivo experiments show that this de novo-designed nanoprobe can selectively enable rapid (4 h postinjection) NIRF imaging with high sensitivity (105colony-forming units) and efficient photothermal therapy (PTT) of MRSA infections in mice. Remarkably, the SiO2-Cy-Van nanoprobes can also afford a long-term tracking (16 days) of the development of MRSA infections, allowing real-time estimation of bacterial load in infected tissues and further providing a possible way to monitor the efficacy of antimicrobial treatment. The strategy of bacteria-activated polyelectrolyte dissociation from nanoparticles proposed in this work could also be used as a general method for the design and fabrication of bacteria-responsive functional nanomaterials that offer possibilities to combat drug-resistant bacterial infections.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yi
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Rao
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Guo
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Weifeng
authors.identifier: 0000-0002-0244-2908
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions , Suzhou 215123, China.
authors.forename: Yong-Qiang
authors.identifier: 0000-0003-1551-3020
authors.initials: YQ
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, China.
authors.forename: Chunying
authors.identifier: 0000-0002-6027-0315
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000628:therapy*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014640:Vancomycin / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D014640:Vancomycin; D012822:Silicon Dioxide
keywords: bacterial infections; bioimaging; photothermal therapy; superbug; theranostic probes