I-Corps: Targeted light activatable nanoparticle to treat metastasized cancer cells

The broader impact/commercial potential of this I-Corps project is the development of phototherapy for peritoneal metastatic cancer treatment. Currently, more than 75,000 cases of peritoneal metastasis are diagnosed in the U.S. each year with poor survival and high recurrence rates. Photoimmunotherapy has recently been approved for treatment of primary tumors and several clinical trials are in progress. However, a significant number of patient deaths result from metastasis, and there is a demand for combination strategies to maximize the benefits of cancer immunotherapy. The proposed technology is designed to simultaneously target and deliver multiple synergistic combination drugs, thus effectively improving treatment outcomes. In addition, light activation of the drug may mediate targeted cancer damage while sparing surrounding healthy tissues. By integrating these capabilities with fluorescence imaging, surgeons and oncologists may monitor drug delivery and customize dosing as needed. This may provide cancer patients with access to the most effective treatment with fewer toxicity-associated hospitalizations. This I-Corps project is based on the development of targeted, light-activated nanoparticle for cancer phototherapy. The proposed nanotechnology is designed to achieve simultaneous delivery and sequential activation of multiple drugs that target all major regions of a cancer cell including the plasma membrane, cytoplasm, and nucleus. It may be used to co-deliver three regimens to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes including therapeutic antibodies (e.g., Cetuximab) that selectively target membrane-bound receptors (e.g., epidermal growth factor receptor, EGFR) for effective photodynamic depolarization of cytosolic organelles (e.g., mitochondria) using light-activatable photosensitizers (e.g., benzoporphyrin derivative), and subsequent release of DNA damaging agents (e.g., topoisomerase inhibitor irinotecan) to induce potent nuclear DNA damage for synergistic outcomes. The proposed technology will be applied to cancers that lead to peritoneal metastasis, such as ovarian cancer and late-stage appendix, gastrointestinal, and colorectal cancers. A successful translation of this technology to the clinic may contribute to improving progression-free survival and overall survival in patients. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.