Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo.


Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 02 2021
Historique:
received: 16 06 2020
revised: 27 11 2020
accepted: 11 12 2020
pubmed: 18 12 2020
medline: 8 7 2021
entrez: 17 12 2020
Statut: ppublish

Résumé

The present work describes the engineering of anti-PSMA peptide-decorated exosome mimetics (EMs) targeting advanced prostate cancer (PC). The targeted EMs were produced from anti-PSMA peptide, WQPDTAHHWATL, expressing U937 monoblastic cells, followed by successive extrusion cycles. The engineered EMs were nanosized, produced at a high yield, and displayed the anti-PSMA peptide, exosomal markers and monocytes proteins on their surface. As anticipated, PSMA-EMs showed increased cellular internalization in PSMA positive PC cell lines (LNCaP and C4-2B), compared to unmodified EMs. Most importantly, higher tumour targeting was observed in solid C4-2B tumours, following intravenous administration, confirming their targeting ability in vivo. Overall, our study indicates that the engineered anti-PSMA peptide-targeted EMs can be a promising drug delivery system for advanced PC.

Identifiants

pubmed: 33333118
pii: S0168-3659(20)30741-0
doi: 10.1016/j.jconrel.2020.12.017
pii:
doi:

Substances chimiques

Antigens, Surface 0
Glutamate Carboxypeptidase II EC 3.4.17.21
Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101-110

Subventions

Organisme : Prostate Cancer UK
ID : CDF12-002
Pays : United Kingdom

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Maja Severic (M)

School of Pharmacy, Queen's University Belfast, United Kingdom.

Guanglong Ma (G)

School of Pharmacy, Queen's University Belfast, United Kingdom.

Sara G T Pereira (SGT)

School of Pharmacy, Queen's University Belfast, United Kingdom.

Amalia Ruiz (A)

School of Pharmacy, Queen's University Belfast, United Kingdom.

Calvin C L Cheung (CCL)

School of Pharmacy, Queen's University Belfast, United Kingdom.

Wafa T Al-Jamal (WT)

School of Pharmacy, Queen's University Belfast, United Kingdom. Electronic address: w.al-jamal@qub.ac.uk.

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Classifications MeSH