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Chembiochem. 2016 Apr 1;17(7):570-5. doi: 10.1002/cbic.201500564. Epub 2016 Feb 19.

New p32/gC1qR Ligands for Targeted Tumor Drug Delivery.

Author information

1
University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Viikinkaari 5E, Helsinki, 00014, Finland.
2
Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
3
Sanford Burnham Prebys Medical Discovery Institute Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.
4
Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
5
Department of Surgery, Columbia University College of Physicians and Surgeons, 1130 St Nicholas Avenue, Suite 217C, New York, NY, 100032, USA.
6
School of Medicine, University of California, Riverside, Riverside, CA, 92521, USA.
7
Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA. Tambet.Teesalu@ut.ee.
8
Sanford Burnham Prebys Medical Discovery Institute Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. Tambet.Teesalu@ut.ee.
9
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. Tambet.Teesalu@ut.ee.

Abstract

Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high-throughput screening of a 50,000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface-functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32-expressing breast tumors in mice. This compound provides a lead for the development of p32-targeted affinity ligands that circumvent some of the limitations of peptide-based probes in guided drug delivery.

KEYWORDS:

cancer; drug delivery; high-throughput screening; nanoparticles; peptides

PMID:
26895508
PMCID:
PMC5433940
DOI:
10.1002/cbic.201500564
[Indexed for MEDLINE]
Free PMC Article

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