Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery.
Amino Acid Sequence
Animals
Apoptosis
Cell Line, Tumor
Drug Delivery Systems
Ferric Compounds
/ chemistry
Fibronectins
/ metabolism
Glioblastoma
/ drug therapy
Humans
Magnetic Resonance Imaging
Metal Nanoparticles
/ chemistry
Mice, Nude
Nanoparticles
/ chemistry
Neoplasms
/ diagnostic imaging
Peptides
/ therapeutic use
Silver
/ chemistry
Tenascin
/ metabolism
Affinity targeting
Extracellular matrix
GBM
Homing peptide
Magnetic resonance imaging
Nanomedicine
Prostate carcinoma
T7 phage display
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
02
04
2019
revised:
08
07
2019
accepted:
18
07
2019
pubmed:
3
8
2019
medline:
24
9
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
Oncofetal fibronectin (FN-EDB) and tenascin-C C domain (TNC-C) are nearly absent in extracellular matrix of normal adult tissues but upregulated in malignant tissues. Both FN-EDB and TNC-C are developed as targets of antibody-based therapies. Here we used peptide phage biopanning to identify a novel targeting peptide (PL1, sequence: PPRRGLIKLKTS) that interacts with both FN-EDB and TNC-C. Systemic PL1-functionalized model nanoscale payloads [iron oxide nanoworms (NWs) and metallic silver nanoparticles] homed to glioblastoma (GBM) and prostate carcinoma xenografts, and to non-malignant angiogenic neovessels induced by VEGF-overexpression. Antibody blockage experiments demonstrated that PL1 tumor homing involved interactions with both receptor proteins. Treatment of GBM mice with PL1-targeted model therapeutic nanocarrier (NWs loaded with a proapoptotic peptide) resulted in reduced tumor growth and increased survival, whereas treatment with untargeted particles had no effect. PL1 peptide may have applications as an affinity ligand for delivery of diagnostic and therapeutic compounds to microenvironment of solid tumors.
Identifiants
pubmed: 31374479
pii: S0142-9612(19)30472-7
doi: 10.1016/j.biomaterials.2019.119373
pii:
doi:
Substances chimiques
Ferric Compounds
0
Fibronectins
0
Peptides
0
Tenascin
0
ferric oxide
1K09F3G675
Silver
3M4G523W1G
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
119373Subventions
Organisme : Wellcome Trust
ID : WT095077MA
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.