Coadministration of a Tumor-penetrating Peptide Enhances the Efficacy of Cancer Drugs

Overview

Journal Science

Specialty Science

Date 2010 Apr 10

PMID 20378772

Citations 403

Authors

Kazuki N Sugahara

Tambet Teesalu

Priya Prakash Karmali

Venkata Ramana Kotamraju

Lilach Agemy

Daniel R Greenwald

Erkki Ruoslahti

Affiliations

Soon will be listed here.

Abstract

Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.

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