In Vitro Cytotoxic Evaluation of Quercetin-Loaded Lecithin-Chitosan Nanoparticles against Colorectal Cancer

Background: The flavonoid quercetin (Qu), which is abundant in nature, can influence cellular signaling, oxidative stress, and inflammation pathways, making it a promising treatment option. However, quercetin's chemical instability and poor water solubility limit its effectiveness in colorectal cancer (CRC) therapy. These challenges are addressed by loading quercetin onto lecithin and chitosan to create Quercetin-loaded Lecithin/Chitosan nanoparticles (Qu-L/CS NPs). This study examines the effects of Qu and Qu-L/CS NPs on Caco-2 CRC cells, comparing their efficacy to doxorubicin (Doxo) as a positive control and normal cells as a negative control. Additionally, the study investigates gene expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), Hairy/Enhancer of split (Hes-1), and Phosphatase and tensin homolog (PTEN), as well as molecular docking of quercetin to selected genes. Methods: Caco-2 cell proliferation, gene expression, and binding affinities were assessed using MTT assays, qRT-PCR, and molecular docking. Results: Both Qu and Qu-L/CS NPs downregulated TNF-α, NF-κB, Hes-1, and PTEN in Caco-2 cells. Cell viability decreased dose-dependently, with IC50 of 6.64 µg/mL (Qu), 6.4 µg/mL (Qu-L/CS NPs), and 2.58 µg/mL (Doxo). Molecular docking revealed superior binding affinities of quercetin for PTEN and NF-κB compared to known inhibitors, indicating stronger target interactions. Conclusion: Qu and Qu-L/CS NPs exert anti-proliferative effects in CRC by suppressing key oncogenic pathways. These findings support further development of quercetin-based nanoformulations as anti-CRC therapeutics.