The central goal of this project is to improve systemic therapies of cancer using soft nanomaterials that can deeply penetrate into tumors and deliver potent anticancer agents the targeted cancer cells, Many small-molecule therapeutics that were highly promising for cancer therapy, eventually fail clinical translation due to toxicity, poor solubility, stability and other delivery related problems. Recent advances in nanoparticle drug carriers provide a unique opportunity to “rescue” these agents enable their clinical application. This is the focal point of our research using nanocarriers that can incorporate such agents, and preferentially deliver them to tumors. Our group has successfully developed a novel platform for drug delivery that uses aqueous polymeric gel nanoparticles, core-shell nanogels (CSNGs) which are manufactured through a proprietary self-assembly process to be readily filled with various drug payloads. These water-swollen particles are practically non-adhesive, which greatly diminishes off-target side effects. CSNGs are unique because they can simultaneously incorporate both water-soluble and water-insoluble drugs and can be engineered to produce optimized product candidates with enhanced drug targeting, drug release, PK, biodistribution, safety and efficacy. Proof of concept has been demonstrated in animal models with targeted CSNGs carrying anti-neoplastic agents to treat tumors. We will focus our research efforts on using CSNGs in the triple negative breast cancer (TNBC), a disease that despite treatment advances, still has a very poor outcome. The specific aims are: 1. Determine how the molecular architecture of polypeptide-based CSNGs correlates with their ability to load, deliver and release therapeutic cargos in triple-negative breast cancer. 2. Determine in vivo PK and biodistribution of CSNGs in murine models of TNBC. 3. Use targeting strategy to understand the mechanism and efficiency of nanogels delivery and to study the cancer biology in TNBC.
|Effective start/end date||8/14/15 → 7/31/20|
- NIH National Cancer Institute (NCI)
Triple Negative Breast Neoplasms
Drug Delivery Systems