Tuesday, August 18, 2015

PEG-PLGA from PolySciTech used to generate nanoparticles for chemoradiotherapy

PolySciTech (www.polyscitech.com) provides a wide variety of PEG-PLGA block copolymers. Recently researchers at University of North Carolina utilized PEG-PLGA from PolySciTech to generate nanoparticles which sequentially release wortmannin followed by docetaxel. Wortmannin acts to inhibit Phosphoinositide 3-kinase activity which reduces cancer metastasis (capability of cancer cells to float freely) and angiogenesis (capability of cancer cells to grow new blood vessels). Docetaxel acts to prevent cellular reproduction and as such has strong chemotherapeutic activity. It was found that delivering both together in sequence increased the effectiveness of the treatment as well as the efficiency of radiotherapy. Read more: Au, Kin Man, Yuanzeng Min, Xi Tian, Longzhen Zhang, Virginia Perello, Joseph M. Caster, and Andrew Z. Wang. "Improving Cancer Chemoradiotherapy Treatment by Dual Controlled Release of Wortmannin and Docetaxel in Polymeric Nanoparticles." (2015). http://pubs.acs.org/doi/abs/10.1021/acsnano.5b02913

“Abstract: Combining molecularly targeted agents and chemotherapeutics is an emerging strategy in cancer treatment. We engineered sub-50 nm diameter di-block copolymer nanoparticles (NPs) that can sequentially release wortmannin (Wtmn, a cell signaling inhibitor) and docetaxel (Dtxl, genotoxic anticancer agent) to cancer cells. These NPs were studied in chemoradiotherapy, an important cancer treatment paradigm, in the preclinical setting. We demonstrated that Wtmn enhanced the therapeutic efficacy of Dtxl and increased the efficiency of radiotherapy (XRT) in H460 lung cancer and PC3 prostate cells in culture. Importantly, we showed that NPs containing both Wtmn and Dtxl release the drugs in a desirable sequential fashion to therapeutic efficacy in comparison to administering each drug alone. An in vivo toxicity study in a murine model validated that NPs containing both Dtxl and Wtmn do not have a high toxicity profile. Lastly, we demonstrated that Dtxl/Wtmn co-encapsulated NPs are more efficient than each single drug loaded NPs or combination of both single drug loaded NPs in chemoradiotherapy using xenograft models. Histopathological studies and correlative studies support that the improved therapeutic efficacy is through changes in signaling pathways (Wtmn) and increased tumor cell apoptosis. Our findings suggest that our nanoparticle system led to a dynamic rewiring of cellular apoptotic pathways and thus a higher therapeutic efficiency.”
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