everal types of biological functions have been reported for Quercetin, such as antioxidant and anticancer activities. The current study aimed to improve the solubility and stability of Quercetin’s nanoemulsions (QuNEs) produced under polar physiologic conditions and to clarify Quercetin’s interaction properties with calf thymus DNA (ctDNA) in its released form. The cytotoxicity of QuNE was analyzed by measuring the MTT assay in MCF-7 cells and caspase-9 gene expression in the HePG2 liver cancer cell line. Also, the ABTS antioxidant assay was performed for evaluating QuNE’s antioxidant activity. QuNE’s interaction with ctDNA was evaluated via running RLS and CD spectroscopy, viscometry, thermal denaturation, thermodynamic parameters (Van’t Hoff and Stern-Volmer diagrams), and molecular docking methods. The QuNE-released Quercetin significantly reduced viability of MCF-7 cells and induced caspase-9 up-regulation in HepG2 cancer cells. Further, compared with unreleased Quercetin, QuNE particles made complexes with ctDNA through hydrophobic interactions. The ΔH0, ΔS0, and binding constant (BC) indices for QuNE-ctDNA were measured at 68.36 KJ.mol-1, 308.42 J.mol-1K-1, and 0.04 × 104 and 2.49 × 104 M-1, respectively. Further, high antioxidant activity was measured for QuNE. QuNE was detected as the DNA groove binder agent. Considering QuNE’s ability in releasing Quercetin near ctDNA, it can be potentially used as an appropriate delivery transporting system which can successfully interact with DNA molecules in a groove binding manner to induce apoptotic effects.

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