Overview

iRGD is a cyclic peptide composed of the amino acid sequence Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys. This peptide has been extensively researched for its ability to enhance the targeting and permeability of cancer treatments. By binding to specific integrins on tumor endothelial cells, iRGD initiates a protease cleavage that activates binding to neuropilin-1, a receptor involved in cell transport processes. This unique mechanism allows iRGD to improve drug delivery to tumor cells, making cancer therapies more effective and less toxic.

Key Benefits of iRGD

• Enhanced Drug Accumulation in Tumor Cells: Increases the permeability of tumor cells, allowing drugs to penetrate deeper and accumulate at higher concentrations.
• Increased Efficacy of Cancer Therapies: Demonstrated up to a 40-fold increase in drug accumulation within tumors, significantly reducing tumor growth and enhancing overall treatment efficacy.
• Reduced Toxicity of Cancer Drugs: Allows for lower drug dosages with equivalent or greater therapeutic effects, minimizing systemic toxicity and side effects.
• Versatile Application: Works with a variety of drug types, including small molecules (e.g., doxorubicin), nanoparticles (e.g., liposomal doxorubicin and nab-paclitaxel), and monoclonal antibodies (e.g., trastuzumab).

Mechanism of Action

iRGD selectively binds integrins present on tumor blood vessels. This binding triggers a proteolytic cleavage that exposes a binding site for neuropilin-1, a receptor that mediates an endocytotic/exocytotic pathway. This pathway increases vascular and tissue permeability specifically in tumors, allowing enhanced uptake of co-administered cancer drugs. This effect is achieved without needing to conjugate the peptide to the drugs, making it a highly adaptable and efficient means of improving drug delivery.

Clinical Research

Tumor Penetration and Drug Efficacy Enhancement

Research on mouse tumor models demonstrated that co-administration of iRGD with various anti-cancer drugs improved vascular and tissue permeability in tumors, allowing drugs to reach extravascular tumor tissue more effectively. By enabling deeper drug penetration, iRGD co-administration increased drug efficacy without additional chemical modification. This has shown promise in enhancing therapeutic outcomes while simultaneously reducing the required drug dose.

Notable Findings:

• Co-administered with doxorubicin, nab-paclitaxel, liposomal doxorubicin, or trastuzumab, iRGD increased drug accumulation within tumors by up to 40 times compared to drugs administered alone.
• Equivalent tumor growth reduction was observed with iRGD co-administration at drug doses one-third of the standard required amount, suggesting a safer and more efficient treatment modality.

Product Information

• Product Name: iRGD (Cancer Targeting Peptide)
• Applications:
  • Enhancing permeability and efficacy of anti-cancer drugs
  • Reducing toxicity of cancer treatments
• Mode of Action: Integrin binding with neuropilin-1 receptor activation for increased tumor cell permeability and drug penetration
• Compatibility: Effective with multiple types of cancer therapies including small molecules, nanoparticles, and monoclonal antibodies