Peptide
iRGD

 

iRGD

iRGD is a cyclic peptide that binds to integrins that are expressed on tumor endothelial cells. Upon binding, a protease cleavage event is activated. When this event is activated the peptide is then able to bind neuropilin-1, activating an endocytotic/exocytotic transport pathway. As a result of this, it is able to hone to tumor cells and make them permeable to transport of many types of cancer therapies. This makes traditional cancer therapies target cells better and makes the therapy less toxic. One study showed that doxorubicin, liposomal doxorubicin, Herceptin trastuzumab or Abraxane nab-paclitaxel had greater drug accumulation in the tumor by up to 40-fold than mice injected with one of the drugs alone. They equaled greater reductions in tumor growth. In all, the drug-peptide combination was as effective as threefold higher doses of drug alone.

CLINICAL RESEARCH:

Co-administration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs
Poor penetration of anti-cancer drugs into tumors can be an important factor limiting their efficacy. Studying mouse tumor models, we show that a previously characterized tumor-penetrating peptide, iRGD (CRGDK/RGPD/EC), increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing co-administered 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, co-administration of iRGD may be a valuable way to enhance the efficacy of anti-cancer drugs while reducing their side effects, a primary goal of cancer therapy research.

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