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Biomaterials. 2019 Oct;219:119373. doi: 10.1016/j.biomaterials.2019.119373. Epub 2019 Jul 19.

Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery.

Author information

1
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Tartu, Estonia.
2
Department of Geology, University of Tartu, 50411, Tartu, Estonia.
3
Department of Neurosurgery, Tartu University Hospital, 50406, Tartu, Estonia.
4
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, 92037, CA, USA; Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, 93106, CA, USA.
5
Department of Biomedicine Translational Cancer Research, University of Bergen, 5020, Bergen, Norway.
6
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Tartu, Estonia; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, 92037, CA, USA; Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, 93106, CA, USA. Electronic address: tambet.teesalu@ut.ee.

Abstract

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.

KEYWORDS:

Affinity targeting; Extracellular matrix; GBM; Homing peptide; Magnetic resonance imaging; Nanomedicine; Prostate carcinoma; T7 phage display

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