ArticleJournal of advanced research2024
Antibody-antibiotic conjugate targeted therapy for orthopedic implant-associated intracellular S. aureus infections.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Quantifying the Long and Short Axes of the External Iliac Lymph Nodes Using Dual-Energy Computed Tomography: A Potential Diagnostic Approach for Periprosthetic Joint Infection - A Prospective Study.Infection and drug resistance · 2024Trial
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Orthogonal Design of a Guanidinocarbonyl Pyrrole-Functionalized Pillar[5]arene-Based Adjuvant for Synergistic Antibacterial Therapy.Advanced healthcare materials · 2026Article
- Antibody-Antibiotic Conjugates: Mechanisms, Clinical Progress, and Next-Generation Strategies Against Multidrug-Resistant Bacterial Infections.MicrobiologyOpen · 2026Review
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- A novel anti-PcrV monoclonal antibody inhibits toxin-mediated cytotoxicity and enhances survival in mouse models ofHuman vaccines & immunotherapeutics · 2025Article
- Novel Therapies for Prosthetic Joint Infections Caused by Methicillin-ResistantPathogens (Basel, Switzerland) · 2025Review
- Next stop, precision: targeted therapies forFuture microbiology · 2025Article
- A deformable SIS/HA composite hydrogel coaxial scaffold promotes alveolar bone regeneration after tooth extraction.Bioactive materials · 2025Article
- Staphylococcus aureus induces mitophagy via the HDAC11/IL10 pathway to sustain intracellular survival.Journal of translational medicine · 2025Article
- Combined Use of External Iliac Lymph Node Count and Bone Scintigraphy for PJI Diagnosis: A Prospective Study.Diagnostics (Basel, Switzerland) · 2024Article
- Precise Clearance of Intracellular MRSA via Internally and Externally Mediated Bioorthogonal Activation of Micro/Nano Hydrogel Microspheres.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An Overview of the Development and Preclinical Evaluation of Antibody-Drug Conjugates for Non-Oncological Applications.Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTreating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells.
objectivesIntroduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus.
methodsThe AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging.
resultsIn vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone.
conclusionsThe application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.
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