| Targeted Delivery of Paclitaxel to EphA2-Expressing Cancer Cells. | |
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MedLine Citation:
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PMID: 23155185 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anti-cancer agents to prostate cancer tumors (1). 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 to vehicle or paclitaxel treatments. CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anti-cancer agents to a variety of tumor types. Translational Relevance: Overexpression of the EphA2 positively correlates with tumor malignancy and poor prognosis. For this reason, EphA2 is an attractive target for cancer cell specific drug delivery. In this study, we report on the development of dYNH, an EphA2 targeting peptide that when coupled to paclitaxel (PTX) has favorable pharmacological properties and possesses powerful anti-tumor activity in vivo. dYNH-PTX may allow for an expanded therapeutic index of paclitaxel as well as precluding the need for complex formulations and long infusion times. |
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Authors:
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Si Wang; Roberta Noberini; John L Stebbins; Swadesh K Das; Ziming Zhang; Bainan Wu; Sayantan Mitra; Sandrine Billet; Ana Fernandez; Neil A Bhowmick; Shinichi Kitada; Paul Fisher; Elena B Pasquale; Maurizio Pellecchia |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-15 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: - ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Cancer Research Center, Sanford-Burnham Medical Research Institute. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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