Novel pH responsive hesperidin nanoformulation exerts anticancer activity on lung adenocarcinoma cells by targeting Akt/mTOR and MEK/ERK pathways

Zinc oxide nanoparticle based drug delivery enhances bioavailability of anticancer drug to the tumor site. We developed novel biocompatible ZnO nanoparticles for the targeted delivery of hesperidin. UV, FT-IR, DLS analysis, SEM and XRD analyses were done to confirm hesperidin loading onto zinc oxide nanoparticles. We also performed crystal violet staining, ROS and live-dead staining assay to check toxicity of hesperidin nanoformulation on A549 lung adenocarcinoma cells. Effect of nanoformulation on protein and gene expression was evaluated. Particle size of formulated ZnO NPs was 3 nm, which increased to 104 nm after hesperidin loading. Hesperidin nanoformulation showed enhanced anticancer, antiproliferative and antimigratory effects on A549 cells with an IC50 concentration of 40 µg/mL. The nanoformulation reduced expression of Akt/mTOR and MEK/ERK signalling proteins and increased the expression of apoptotic markers. Hesperidin nanoformulation also upregulated the expression of apoptotic genes such as Bax, p53 and decreased the expression of anti-apoptotic gene Bcl2. Hesperidin nanoformulation and its biological activities.