PXD021926

PXD021926 is an original dataset announced via ProteomeXchange.

Title	A novel enzyme-mediated method for covalent surface modification of extracellular vesicles to achieve targeted drug delivery
Description	Natural extracellular vesicles (EVs) are ideal drug carriers due to their remarkable biocompatibility. Their delivery specificity can be achieved by the conjugation of targeting ligands. However, existing methods to engineer target-specific EVs are tedious or inefficient, having to compromise between harsh chemical treatments or transient interactions. Here, we describe a novel method for the covalent conjugation of EVs with high copy numbers of targeting moieties using protein ligases. Conjugation of EVs with either an epidermal growth factor receptor (EGFR)-targeting peptide or anti-EGFR nanobody facilitates their accumulation in EGFR-positive cancer cells, both in vitro and in vivo. Systemic delivery of paclitaxel by EGFR-targeting EVs at a low dose significantly increases drug efficacy in a xenografted mouse model of EGFR-positive lung cancer. The method is also applicable to the conjugation of EVs with peptides and nanobodies targeting other receptors, such as HER2 and SIRP alpha, and the conjugated EVs can deliver RNA in addition to small molecules, supporting the versatile application of EVs in cancer therapies. This simple, yet efficient and versatile method for the stable surface modification of EVs bypasses the need for genetic and chemical modifications, thus facilitating safe and specific delivery of therapeutic payloads to target cells.
HostingRepository	PRIDE
AnnounceDate	2021-03-24
AnnouncementXML	Submission_2021-03-24_01:48:18.707.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Kappei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-12 06:55:28	ID requested
⏵ 1	2021-03-24 01:48:19	announced

Pham TC, Jayasinghe MK, Pham TT, Yang Y, Wei L, Usman WM, Chen H, Pirisinu M, Gong J, Kim S, Peng B, Wang W, Chan C, Ma V, Nguyen NTH, Kappei D, Nguyen XH, Cho WC, Shi J, Le MTN, Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery. J Extracell Vesicles, 10(4):e12057(2021) [pubmed]

submitter keyword: extracellular vesicles, RBCEVs, drug delivery

Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS)
contact email	dennis.kappei@nus.edu.sg
lab head
Dennis Kappei
contact affiliation	Cancer Science Institute of Singapore
contact email	dennis.kappei@nus.edu.sg
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD021926

PRIDE project URI

• PRIDE
  1. PXD021926
     1. Label: PRIDE project
     2. Name: A novel enzyme-mediated method for covalent surface modification of extracellular vesicles to achieve targeted drug delivery