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Clin Cancer Res. 2013 Jan 1;19(1):128-37. doi: 10.1158/1078-0432.CCR-12-2654. Epub 2012 Nov 15.

Targeted delivery of paclitaxel to EphA2-expressing cancer cells.

Author information

1
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 90237, USA.

Abstract

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.

PMID:
23155185
PMCID:
PMC3537892
DOI:
10.1158/1078-0432.CCR-12-2654
[Indexed for MEDLINE]
Free PMC Article
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