title: Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of α3 integrin-expressing human tumors.
abstract: BACKGROUND
  α3β1 integrin is overexpressed in several types of human cancer and is associated with poor prognosis, metastasis, and resistance to cancer treatment. We previously identified a cyclic peptide ligand LXY1 that specifically binds to the α3β1 integrin on human glioblastoma U-87MG cells. Here, we optimized LXY1 through one-bead one-compound combinatorial library screening and site-specific modifications to improve its in vivo binding property.
  
  
  METHODS
  Three bead libraries were synthesized and whole-cell binding assays were performed. The binding capacity of individual peptide ligands against different tumor cells was determined by flow cytometry and confirmed by optical imaging. A complex joining biotinylated ligand with streptavidin-Cy5.5 was used for in vivo target imaging in both subcutaneous and orthotopic U-87MG xenograft mouse models.
  
  
  RESULTS
  LXY30, a cyclic peptide with the sequence cdG-Phe(3,5-diF)-G-Hyp-NcR, emerged as the most potent and selective ligand for the α3 subunit of α3β1 integrin with improved in vitro and in vivo tumor-targeting effects compared to LXY1 in U-87MG cells. LXY30 is considerably stable in plasma as demonstrated in an in vitro stability study in 90 % human plasma. LXY30 also binds to several other known α3β1 integrin-expressing glioblastoma, lung, and breast cancer cell lines with various affinities.
  
  
  CONCLUSIONS
  Our data support further investigating the role of LXY30 as a human tumor-targeting peptide ligand for systemic and intracranial delivery of imaging agents and cancer therapeutics.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, 95817, USA.|University of California Davis Comprehensive Cancer Center, Sacramento, CA, 95817, USA.|Veterans Affairs Northern California Health Care System, Mather, CA, 95655, USA.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Bononi
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Lac
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Ivy A
authors.initials: IA
authors.lastname: Kekessie
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Anisha
authors.initials: A
authors.lastname: Mazloom
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Tran
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, 95817, USA.|The College of the University of Chicago, Chicago, IL, 60602, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.|Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, 95817, USA.|University of California Davis Comprehensive Cancer Center, Sacramento, CA, 95817, USA.
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA. rwliu@ucdavis.edu.|University of California Davis Comprehensive Cancer Center, Sacramento, CA, 95817, USA. rwliu@ucdavis.edu.
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Liu
keywords: Cancer-targeting peptide; Glioblastoma; One-bead one-compound combinatorial peptide library; Optical imaging; α3β1 integrin