title: New p32/gC1qR Ligands for Targeted Tumor Drug Delivery.
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.
authors.affiliation: University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Viikinkaari 5E, Helsinki, 00014, Finland.|Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Lauri
authors.initials: L
authors.lastname: Paasonen
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Braun
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.|Sanford Burnham Prebys Medical Discovery Institute Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Thomas D Y
authors.initials: TD
authors.lastname: Chung
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.|Department of Surgery, Columbia University College of Physicians and Surgeons, 1130 St Nicholas Avenue, Suite 217C, New York, NY, 100032, USA.
authors.forename: Kazuki N
authors.initials: KN
authors.lastname: Sugahara
authors.affiliation: University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Viikinkaari 5E, Helsinki, 00014, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.
authors.forename: Bainan
authors.initials: B
authors.lastname: Wu
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.|School of Medicine, University of California, Riverside, Riverside, CA, 92521, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA.|Sanford Burnham Prebys Medical Discovery Institute Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA, 93027, USA. Tambet.Teesalu@ut.ee.|Sanford Burnham Prebys Medical Discovery Institute Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. Tambet.Teesalu@ut.ee.|Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. Tambet.Teesalu@ut.ee.
authors.forename: Tambet
authors.identifier: http://orcid.org/0000-0002-9458-6385
authors.initials: T
authors.lastname: Teesalu
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy*; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D024101:Mitochondrial Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010456:Peptides, Cyclic / Q000008:administration & dosage*
chemical_list: C000613561:4014008 compound; D000631:Aminopyridines; D000970:Antineoplastic Agents; C087299:C1QBP protein, human; D002352:Carrier Proteins; D005029:Ethylenediamines; D008024:Ligands; C533969:LyP-1 peptide; D024101:Mitochondrial Proteins; D010456:Peptides, Cyclic
keywords: cancer; drug delivery; high-throughput screening; nanoparticles; peptides