Amanda Fam with Dr. G. Mike Makrigiorgos (DFCI)
Flavonoids are compounds found in plants that possess therapeutic properties. There is accumulating evidence that many flavonoids exert anticancer activity, however, the molecular mechanisms responsible for this effect have not been fully elucidated yet. Recent studies have shown that flavonoids like Hesperetin can bind strongly to the ACE2 receptor. ACE2 is largely expressed by epithelial cells of the lung, kidney, heart, blood vessels, and intestine and may have different roles in different cancer models. Our research target is to evaluate the delivery of flavonoids in lung cancer cells to evaluate the cytotoxic ability on lung cancer cells and compare it with normal lung cells. We will investigate the use of nanoparticle drones (nanodrones) to deliver flavonoids to cancer and normal cells, to evaluate the uptake and duration of the presence in the cells. Nanodrones are smart nanoparticles specifically designed with targeting moieties to deliver drugs to different sites, and are sensitive to a stimulus, such as photons, temperature, or pH, to then respond in active ways including releasing a drug payload or generating a therapeutic action or a signal allowing for imaging. The nanodrones loaded with flavonoids will be investigated for targeting A549 and Calu-2 lung cancer cells with and without radiotherapy. Furthermore, preliminary studies have shown an increased damage enhancement factor for nanoparticles in in-vivo studies when they are delivered through inhalation as opposed to intravenous administration. The overall hypothesis is that Flavonoid loaded ACE2 Nanodrones will inhibit the progression of lung tumor cells and amplify damage to the tumors during radiotherapy.