Tatiana Hurtado de Mendoza
Sanford Burnham Prebys Medical Discovery Institute, USA
Title: iRGD, a tumor-penetrating peptide for tumor-specific drug delivery
Biography
Biography: Tatiana Hurtado de Mendoza
Abstract
Delivering cancer drugs specifically to tumors and deep into tumor tissue against the high interstitial pressure is a major hurdle in cancer therapy. The iRGD drug delivery system may provide a solution. The iRGD peptide (CRGDK/RGPD/EC) was identified by phage display against metastatic prostate cancers (Sugahara et al, Cancer Cell, 2009). iRGD carries a tumor-specific RGD motif, which recognizes av integrins that are highly expressed on tumor vasculature and tumor cells, and an RXXK/R CendR motif, which binds to a tissue-penetration receptor neuropilin-1. Importantly, the tissue penetration pathway involves an energy-dependent active transport system, which relies on a mechanism similar to macropinocytosis (Pang et al, Nature Communications, 2014). This unique property allows iRGD to accomplish tumor-penetrating delivery of drugs by simple co-administration (Sugahara et al, Science, 2010). Thus, the therapeutic index of various drugs can be enhanced without any chemical modification of the drugs. In fact, iRGD enhanced tumor-specific accumulation and anti-tumor effects of various types of systemic drugs including small chemicals, nanodrugs, and antibodies in a number of tumor types. Our recent studies have revealed that iRGD alone has anti-metastatic effects when delivered intravenously, providing an additional benefit of using the iRGD system for cancer therapy (Sugahara et al, Molecular Cancer Therapy, 2015). In addition, the iRGD co-administration system is effective not only for systemic cancer therapy, but also for intraperitoneal chemotherapy for peritoneal carcinomatosis (Sugahara et al, Journal of Controlled Release, 2015). A brief overview and recent advances of the iRGD system will be discussed at the meeting