Chitosan-functionalized mesoporous silica nanoparticles co-loaded with chrysin and quercetin: a potent strategy against lung cancer cells.

Lung cancer (LC) represents a major and growing challenge in global healthcare, necessitating the exploration of innovative therapeutic strategies. In this context, nanoparticles (NPs) have emerged as promising platforms for enhancing treatment efficacy and improving patient outcomes. The present study investigated the cytotoxic effects of chitosan-functionalized mesoporous silica nanoparticles (MSNs) co-loaded with chrysin (Chr) and quercetin (Qur)—denoted as Chr–Qur@MSNs–Chi—on A549 lung cancer cells. Chr–Qur@MSNs–Chi NPs were synthesized and characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Cell viability and apoptosis-related gene expression were evaluated using the MTT assay and quantitative real-time PCR (qRT-PCR), respectively.The synthesized NPs were spherical, with an average size range of 80–110 nm, and exhibited no detectable impurities. The DLS analysis indicated a particle size of approximately 110 nm and a zeta potential of − 36.5 mV. The MTT assay revealed IC₅₀ values of 1 µM and 2 µM after 24 and 48 h of treatment, respectively. Furthermore, Chr–Qur@MSNs–Chi induced greater cell cycle arrest at the G0/G1 phase compared to the free Chr–Qur combination. Gene expression analysis demonstrated significant upregulation of p53, Bax, and Fas (2.1-, 2.2-, and 2.4-fold, respectively), alongside downregulation of Cyclin D1, pRB, and Bcl-2 (0.6-, 0.8-, and 0.7-fold, respectively), indicating strong apoptotic effects (P < 0.001). These findings suggest that Chr–Qur@MSNs–Chi nanoparticles exhibit potent anticancer activity against A549 human lung cancer cells, likely through the induction of apoptosis and modulation of apoptosis-related gene expression pathways.