FLAVCAN · Innovative Flavonoid-based Nanoparticles (Flav-NPs) to Fight Against Colorectal Cancer (FLAVCAN)

Colorectal cancer is among the most lethal and prevalent malignancies in the world. Current treatment has limitations, such as adverse effects, drug resistance, metastasis, and recidivism. Flavonoids such as Apigenin, Epigallocatechin-3-gallate, and Quercetin have demonstrated anticancer effects and alternatives for new treatments. Flavonoids can suppress tumor growth, induce apoptosis, inhibit angiogenesis, and modulate cellular signaling pathways in development and progression. Multiple flavonoids administrated simultaneously potentially enhance their biological activities, improving the local effect and instigating a synergistic inhibitory effect on cancer cell viability, increasing apoptosis, decreasing proliferation, and causing the arrest of the chemoresistant cells. Flavonoids are challenging to use orally for therapeutic purposes due to their molecular instability and insufficient delivery to the distal portions of the intestine. This project uses a microfluidic platform to identify a potent flavonoid combinatory nanoformulation-based polysaccharide (cellulose derivates) for oral administration. Flav-NPs can enhance chemical stability, accurately control the release of flavonoids, and potentially overcome digestion factors. Flav-NPs can impact multidimensional mechanisms of anticancer action to more effective therapeutic, reduced cellular proliferation, and invasiveness at different cancer stages. Pre-clinical methodologies will be applied to characterize, and stability in vitro digestion will be evaluated. Spheroid and organoid models will determine cell viability and anticancer efficacy. A gut-on-a-chip model will also be developed to observe the effects of Flav-NPs in a simulated intestinal microenvironment tumor. The simplicity of manufacturing and the feasibility of large-scale production of the supplement and nutraceuticals indicate that the proposal can be applied clinically, promoting European scientific excellence and improving my research career.