Document Detail

Targeted delivery of paclitaxel to EphA2-expressing cancer cells.
MedLine Citation:
PMID:  23155185     Owner:  NLM     Status:  MEDLINE    
PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system.
EXPERIMENTAL DESIGN: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo.
RESULTS: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments.
CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types.
Si Wang; Roberta Noberini; John L Stebbins; Swadesh Das; Ziming Zhang; Bainan Wu; Sayantan Mitra; Sandrine Billet; Ana Fernandez; Neil A Bhowmick; Shinichi Kitada; Elena B Pasquale; Paul B Fisher; Maurizio Pellecchia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-15
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  19     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-06-18     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  128-37     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents, Phytogenic / administration & dosage*,  chemistry
Disease Models, Animal
Drug Delivery Systems*
Gene Expression
Neoplasms / drug therapy,  genetics*,  pathology
Neovascularization, Pathologic / drug therapy,  genetics
Paclitaxel / administration & dosage*,  chemistry
Peptides* / chemistry
Receptor, EphA2 / genetics*,  metabolism
Transplantation, Homologous
Tumor Burden / drug effects
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Peptides; 33069-62-4/Paclitaxel; EC, EphA2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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