Thursday, August 20, 2015

PLGA-Rhodamine from PolySciTech used as part of colorectal cancer therapy development


PolySciTech (www.polyscitech.com) provides a wide array of fluorescently conjugated nanoparticles. Recently PLGA-Rhodamine (AV11) from PolySciTech was used to track death-receptor 5 targeted nanoparticles for colorectal cancer therapy. Using the death-receptor, which is typically targeted to initiate apoptosis, as a target for nanotherapy represents a novel method of delivery chemotherapeutics to cancer cells. Read more: Schmid, Daniela, Francois Fay, Donna M. Small, Jakub Jaworski, Joel S. Riley, Diana Tegazzini, Cathy Fenning et al. "Efficient Drug Delivery and Induction of Apoptosis in Colorectal Tumors Using a Death Receptor 5-Targeted Nanomedicine." Molecular Therapy (2014). http://www.nature.com/mt/journal/vaop/ncurrent/full/mt2014137a.html
“Abstract: Death Receptor 5 (DR5) is a pro-apoptotic cell-surface receptor that is a potential therapeutic target in cancer. Despite the potency of DR5-targeting agents in preclinical models, the translation of these effects into the clinic remains disappointing. Herein, we report an alternative approach to exploiting DR5 tumor expression using antibody-targeted, chemotherapy-loaded nanoparticles. We describe the development of an optimized polymer-based nanotherapeutic incorporating both a functionalized polyethylene glycol (PEG) layer and targeting antibodies to limit premature phagocytic clearance whilst enabling targeting of DR5-expressing tumor cells. Using the HCT116 colorectal cancer model, we show that following binding to DR5, the nanoparticles activate caspase 8, enhancing the anti-tumor activity of the camptothecin payload both in vitro and in vivo. Importantly, the combination of nanoparticle-induced DR5 clustering with camptothecin delivery overcomes resistance to DR5-induced apoptosis caused by loss of BAX or overexpression of anti-apoptotic FLIP. This novel approach may improve the clinical activity of DR5-targeted therapeutics while increasing tumor-specific delivery of systemically toxic chemotherapeutics.”
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