Novel Targeted System to Deliver Chemotherapeutic Drugs to EphA2-expressing Cancer Cells

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2012 Feb 15

PMID 22329578

Citations 46

Authors

Si Wang

William J Placzek

John L Stebbins

Sayantan Mitra

Roberta Noberini

Mitchell Koolpe

Ziming Zhang

Russell Dahl

Elena B Pasquale

Maurizio Pellecchia

Affiliations

Soon will be listed here.

Abstract

The efficacy of anticancer drugs is often limited by their systemic toxicities and adverse side effects. We report that the EphA2 receptor is overexpressed preferentially in several human cancer cell lines compared to normal tissues and that an EphA2 targeting peptide (YSAYPDSVPMMS) can be effective in delivering anticancer agents to such tumors. Hence, we report on the synthesis and characterizations of a novel EphA2-targeting agent conjugated with the chemotherapeutic drug paclitaxel. We found that the peptide-drug conjugate is dramatically more effective than paclitaxel alone at inhibiting tumor growth in a prostate cancer xenograft model, delivering significantly higher levels of drug to the tumor site. We believe these studies open the way to the development of a new class of therapeutic compounds that exploit the EphA2 receptor for drug delivery to cancer cells.

Citing Articles

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Nuclear Delivery of Nanoparticle-Based Drug Delivery Systems by Nuclear Localization Signals.

Nie Y, Fu G, Leng Y Cells. 2023; 12(12).

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Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors.

Santana-Viera L, Dassie J, Rosas-Lapena M, Garcia-Monclus S, Chicon-Bosch M, Perez-Capo M Mol Ther Nucleic Acids. 2023; 32:758-772.

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CuAAC ensembled 1,2,3-triazole linked nanogels for targeted drug delivery: a review.

Singh G, Majeed A, Singh R, George N, Singh G, Gupta S RSC Adv. 2023; 13(5):2912-2936.

PMID: 36756399 PMC: 9847229. DOI: 10.1039/d2ra05592a.

Targefrin: A Potent Agent Targeting the Ligand Binding Domain of EphA2.

Baggio C, Udompholkul P, Gambini L, Pellecchia M J Med Chem. 2022; 65(22):15443-15456.

PMID: 36331527 PMC: 9706575. DOI: 10.1021/acs.jmedchem.2c01391.

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