Lung cancer is the largest cancer killer of both men and women in the United States. Discovery of ligands specific to receptor(s) on a surface of a lung cancer cell will impact clinical issues including functional diagnosis and cell-specific drug delivery. Our overall goal is to generate a panel of cell specific molecules that could be used to classify tumor types and then be exploited for targeted delivery of therapeutics. Using phage display technologies, my laboratory has developed platform methodologies to isolate peptides that bind to and mediate uptake into specific cells. We have successfully identified cell-specific targeting peptides for 30 different cell types, including 7 cancer cell lines. The isolated peptides display remarkable cell-specificities, even among similar cells, and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. This high discriminating power suggests that peptides could be identified that selectively bind to different tumor types, even those with similar classifications. We propose to isolate cell-targeting peptides for 16 different lung cancer lines and then utilize these peptides as diagnostic and tumor specific delivery reagents. These peptides will be assayed for affinity and cell-specificity. Efforts will be directed towards translating the targeting phage into small molecule targeting reagents and these peptide scaffolds will be utilized to deliver therapeutics to tumor cells both in vitro and in vivo. The cell specificity demonstrated by these peptides indicates that they are recognizing distinct cell surface receptors that may be of clinical value as biomarkers for lung cancer. Thus, we will utilize the peptides to identify the cellular these unique cellular features. We will then explore the expression patterns of the receptor on a panel of human lung cancer tissues by immunohistochemistry and compare this with the expression level in matched normal tissues. Achieving our goals will impact lung cancer diagnosis and treatment as well as solving general challenges in the field of targeted drug delivery.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA106646-01A2
Application #
6983025
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Song, Min-Kyung H
Project Start
2005-06-07
Project End
2010-04-30
Budget Start
2005-06-07
Budget End
2006-05-31
Support Year
1
Fiscal Year
2005
Total Cost
$363,241
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
McGuire, Michael J; Gray, Bethany Powell; Li, Shunzi et al. (2014) Identification and characterization of a suite of tumor targeting peptides for non-small cell lung cancer. Sci Rep 4:4480
Gray, Bethany Powell; Li, Shunzi; Brown, Kathlynn C (2013) From phage display to nanoparticle delivery: functionalizing liposomes with multivalent peptides improves targeting to a cancer biomarker. Bioconjug Chem 24:85-96
Guthi, Jagadeesh Setti; Yang, Su-Geun; Huang, Gang et al. (2010) MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells. Mol Pharm 7:32-40
Brown, Kathlynn C (2010) Peptidic tumor targeting agents: the road from phage display peptide selections to clinical applications. Curr Pharm Des 16:1040-54
Huang, Gang; Zhang, Chunfu; Li, Shunzi et al. (2009) A Novel Strategy for Surface Modification of Superparamagnetic Iron Oxide Nanoparticles for Lung Cancer Imaging. J Mater Chem 19:6367-6372
Prudkin, Ludmila; Liu, Diane D; Ozburn, Natalie C et al. (2009) Epithelial-to-mesenchymal transition in the development and progression of adenocarcinoma and squamous cell carcinoma of the lung. Mod Pathol 22:668-78
McGuire, Michael J; Li, Shunzi; Brown, Kathlynn C (2009) Biopanning of phage displayed peptide libraries for the isolation of cell-specific ligands. Methods Mol Biol 504:291-321
Li, Shunzi; McGuire, Michael J; Lin, Mai et al. (2009) Synthesis and characterization of a high-affinity {alpha}v{beta}6-specific ligand for in vitro and in vivo applications. Mol Cancer Ther 8:1239-49
Guan, Huili; McGuire, Michael J; Li, Shunzi et al. (2008) Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of alpha(v)beta(6)-positive cancers. Bioconjug Chem 19:1813-21
Elayadi, Anissa N; Samli, Kausar N; Prudkin, Ludmila et al. (2007) A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer. Cancer Res 67:5889-95

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