(584g) Triple Combination Nanochemoprevention of Breast Cancer

According to the American Cancer Society a total of 1,638,910 new cancer cases and 577,190 deaths from cancer are projected to occur in the United States by the end of 2012. There is a dire need for better strategies to prevent, diagnose and treat this deadly disease.  Widespread use of chemopreventive agents has been hampered by both, real and perceived toxicities associated with these agents, which are small molecules with poor bioavailability.   Nanochemoprevention, which involves use of nanoparticles for delivery of chemopreventive agents, is an emerging field that has shown some promise for cancer prevention by improving the bioavailability and reducing toxicity associated with these drugs. We have developed theranostic nanometer-sized constructs that encapsulate multiple promising chemopreventive agents together with a fluorescent dye for tracking drug delivery. Nanoconstruct synthesis and drug encapsulation were characterized, and the effects of chemopreventive nanoconstructs in both monolayer and 3D cell cultures were studied and compared in normal and cancer cell lines. Our results indicate larger effects on cancer cell lines than on normal and that chemopreventive nanoconstructs inhibit the formation of cancer cell acini in 3D cell culture. We have also investigated the chemopreventive efficacy of the nanoconstructs in mouse models, following pharmacokinetic, toxicity and biodistribution studies that showed extended blood circulation half-life and high tolerability of the nanoconstructs compared to free drugs. Preclinical evaluation of a triple combination nanochemoprevention approach against breast cancer will be presented.