Neutrophil Hitchhiking Enhances Liposomal Dexamethasone Therapy of Sepsis
Source abstract
Abstract
Sepsis is characterized by a dysregulated immune response and is very difficult to treat. In the cecal ligation and puncture (CLP) mouse model, we show that nanomedicines can effectively alleviate systemic and local septic events by targeting neutrophils. Specifically, by decorating the surface of clinical-stage dexamethasone liposomes with cyclic arginine-glycine-aspartic acid (cRGD) peptides, we promote their engagement with neutrophils in the systemic circulation, leading to their prominent accumulation at primary and secondary sepsis sites. cRGD-targeted dexamethasone liposomes potently reduce immature circulating neutrophils and neutrophil extracellular traps in intestinal sepsis induction sites and the liver. Additionally, they mitigate inflammatory cytokines systemically and locally while preserving systemic IL-10 levels, contributing to lower IFN-γ/IL-10 ratios as compared to control liposomes and free dexamethasone. Our strategy addresses sepsis at the cellular level, illustrating the use of neutrophils both as a therapeutic target and as a chariot for drug delivery.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Immune Response and Inflammation · Sepsis Diagnosis and Treatment · S100 Proteins and Annexins
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen 52074, Germany
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena 07747, Germany
Medical Faculty, Friedrich-Schiller-University, Jena 07747, Germany
Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen 52074, Germany
Department of Intensive and Intermediate Care Medicine, RWTH Aachen University Hospital, Aachen 52074, Germany
Department of Medicine III, Medical Faculty, RWTH Aachen University Hospital, Aachen 52074, Germany
Department of Pharmaceutics, Faculty of Science, Utrecht University, Utrecht 3584 CG, The Netherlands
Center for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen 52074, Germany
Funding
European Research Council · Medizinische Fakult?t, RWTH Aachen University · Deutsche Forschungsgemeinschaft
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