title: Cutting edge: Humanized nano-proresolving medicines mimic inflammation-resolution and enhance wound healing.
abstract: Endogenous microparticles (MPs) were systematically profiled during the time course of self-limited inflammation. Precursors for specialized proresolving lipid mediators were identified in MPs from inflammatory exudates using liquid chromatography tandem mass spectrometry-based metabolomics. Hence, we postulated that formation of anti-inflammatory and proresolving lipid mediators could underlie beneficial effects attributed to MPs and that this process could serve as a basis for biomimicry. Using human neutrophil-derived MPs, we constructed novel nanoparticles (NPs) containing aspirin-triggered resolvin D1 or a lipoxin A(4) analog. Enriched NPs dramatically reduced polymorphonuclear cell influx in murine peritonitis, shortened resolution intervals, and exhibited proresolving actions accelerating keratinocyte healing. The enriched NPs protected against inflammation in the temporomandibular joint. These findings indicate that humanized NPs, termed nano-proresolving medicines, are mimetics of endogenous resolving mechanisms, possess potent beneficial bioactions, can reduce nanotoxicity, and offer new therapeutic approaches.
authors: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Lucy V
authors: LV
authors: Norling
authors: Matthew
authors: M
authors: Spite
authors: Rong
authors: R
authors: Yang
authors: Roderick J
authors: RJ
authors: Flower
authors: Mauro
authors: M
authors: Perretti
authors: Charles N
authors: CN
authors: Serhan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001241:Aspirin; D002465:Cell Movement / Q000187:drug effects; D002853:Chromatography, Liquid; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000517:prevention & control; D015603:Keratinocytes / Q000187:drug effects; D008055:Lipids / Q000494:pharmacology; D044045:Lipoxins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008863:Microspheres; D018716:Molecular Mimicry; D053758:Nanoparticles / Q000627:therapeutic use*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology; D053719:Tandem Mass Spectrometry; D013704:Temporomandibular Joint / Q000187:drug effects / Q000276:immunology; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D008055:Lipids; D044045:Lipoxins; C040527:lipoxin A4; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D001241:Aspirin