(590a) Polymeric Nanodevices to Tackle Cancer: From Prevention to Treatments

According to the 2008 World Cancer Report, at least 11.4 million people per year are projected to die worldwide by 2015 despite the ongoing fight against cancer. This presentation will highlight the current research of our group in an effort to improve current intervention methods against cancer development. The major thrusts of our cancer research include 1) local, transdermal delivery of chemo-preventive medicine and 2) targeted drug delivery via novel nanocarriers. For the transdermal delivery, we have found that polyamidoamine (PAMAM) dendrimer nanoparticles (NPs) substantially enhances, by more than 4-fold, skin penetration of chemo-preventive medicine such as tamoxifen metabolites. Although proven efficacy in breast cancer prevention, oral administration of the tamoxifen metabolites has been often declined by risk-eligible women due to reported side effects by systemic exposure. The novel dendrimer NP-based penetration enhancer therefore provides an excellent alternative that enables highly effective local, topical delivery of the drugs with reduced or potentially eliminated toxic side effects. For targeted drug delivery, dendrons (a branch of the dendrimers) have been utilized as a component of a novel nanocarrier system to take advantage of their unique properties such as: i) well-defined chemical structure; ii) highly localized peripheral functional groups enabling optimal multivalent binding effect; and iii) one core reactive site providing site-specific co-polymerization, resulting in amphiphlic dendrons. By engineering the amphiphilic dendron-based building blocks, we have achieved enhanced targeting efficacy via strong multivalent effect as well as high drug payload through self-assembled supramolecular structures. The novel dendron-based nanocarrier system provides a platform technology that may be useful targeted delivery of multiple drugs to cancer cells at high specificity.