University of North Carolina, Chapel Hill —Targeted Core Shell Nanogels for Triple Negative Breast Cancer
Principal Investigators: Alexander V. Kabanov, Ph.D., D.Sc., Tatiana Bronich, Ph.D. (University of Nebraska Medical Center), and Rihe Liu, Ph.D.
Co-Investigators: Sergei Sheiko, Ph.D., Andrew Wang, M.D., and William Zamboni, Ph.D.
The goal of this project is to improve systemic therapies of cancer using soft nanomaterials that can penetrate deep into tumors and deliver potent anticancer agents to targeted cancer cells. We have developed a novel platform for drug delivery that uses aqueous polymeric gel nanoparticles termed core-shell nanogels (CSNGs). CSNGs are manufactured through a proprietary self-assembly process and can be readily filled with various drug payloads. They are water-swollen and are practically non-adhesive, which may diminish their off-target side effects. We hypothesize that
- the systemic and tumor flow dynamics of CSNGs will be a function of their molecular architecture and mechanical properties and
- that these properties can be rationally controlled to modify the PK, distribution and tumor penetration of the CSNGs and the drugs they deliver.
We will focus our research efforts on using CSNGs for triple negative breast cancer (TNBC), a disease that, despite treatment advances, still has a very poor outcome. As disease-targeting strategies, we will use the novel single-domain polypeptide antagonists of the EGFR and HER3 that are frequently overexpressed in TNBC and are associated with a higher risk of mortality in TNBC.
The specific aims of our work involve:
- Determine how the molecular architecture and mechanical properties of polypeptide-based CSNGs affects their ability to load, deliver and release therapeutic cargos;
- Determine how the structure and mechanical properties of the drug-loaded CSNGs affect the in vivo PK and tumor distribution of the drugs and nanogels in murine models of TNBC;
- Develop EGFR and HER3 targeted drug-loaded CSNGs with maximal tumor penetration, maximal delivery of drug payload to tumors and potent anti-tumor activity in TNBC.
These integrative efforts will address major barriers in developing nanotechnology platforms for the treatment of TNBC, and facilitate understanding of the cancer biology and the mechanisms of in vivo delivery.
We assembled a cross-disciplinary team of physician-scientists and experts in nanotechnology and pharmacology. Specifically, we encompass expertise in polymer-based drug delivery (Kabanov and Bronich), cancer targeting peptides (Liu), soft materials mechanics (Sheiko), oncology (Wang), and pharmacology (Zamboni).