PXD033512

PXD033512 is an original dataset announced via ProteomeXchange.

Title	Engineered synthetic eukaryotic vesicles as anti-inflammatory drug delivery system to target Myd88
Description	Mesenchymal stem cells (MSC) secrete naturally extracellular vesicles (EV) with a regenerative profile, and an increasing number of studies have focused on the employment of EV for therapeutic drug delivery. However, EV are usually produced by the cells at low quantities and packed with unnecessary cytoplasmic components that are unfavorable for further drug loading. In this study, we developed a simple vesicle generation process from the cell membranes directly, after which they are called synthetic eukaryotic vesicles (SyEV or reNV). We hypothesized that MSC-derived SyEV can be efficiently loaded with an anti-inflammatory drug and the loaded vesicles can strongly suppress bacterial outer membrane vesicle (OMV)-induced sepsis. SyEV were generated from MSC membranes through serial extrusion, ionic stress and subsequent revesiculation, leading to high yield and purity with very few cytosolic contaminants. When these SyEV were given to macrophages and mice exposed to OMV, the release of pro-inflammatory cytokines was significantly inhibited comparable to natural EV. Then, we encapsulated SyEV with a peptide targeting Myd88 and showed the enhanced therapeutic potential of the loaded vesicles in OMV-induced macrophages. Further, in vivo study indicated that the peptide-encapsulated SyEV could dramatically suppress cytokine release into the systemic circulation via a synergistic way. Taken together, these data suggest that SyEV-based therapeutics is a highly interesting platform to deliver an advanced therapeutic drug for the treatment of inflammatory diseases without severe side effects.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:42:32.529.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evelin Berger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-28 01:14:14	ID requested
1	2023-03-11 03:51:23	announced
⏵ 2	2023-11-14 08:42:33	announced	2023-11-14: Updated project metadata.

Park KS, Bergqvist M, L, ä, sser C, L, ö, tvall J, Targeting Myd88 using peptide-loaded mesenchymal stem cell membrane-derived synthetic vesicles to treat systemic inflammation. J Nanobiotechnology, 20(1):451(2022) [pubmed]

submitter keyword: mesenchymal stem cells, extracellular vesicles, therapeutic drug delivery, quantitative proteomics,human

Carina Sihlbom
contact affiliation	Proteomics Core facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
contact email	Carina.sihlbom@gu.se
lab head
Evelin Berger
contact affiliation	University of Gothenburg
contact email	evelin.berger@gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033512
     1. Label: PRIDE project
     2. Name: Engineered synthetic eukaryotic vesicles as anti-inflammatory drug delivery system to target Myd88