LAUSR

Abstract Overexpression of nuclear factor E2–related factor 2 (Nrf2) contributes to the chemotherapeutic resistance of non–small-cell lung cancer (NSCLC). Docetaxel (DTX) is widely used for chemotherapy of NSCLC. However, resistance to DTX often result in failure of chemotherapy. This study aimed to evaluate the ability of hyaluronic acid-based nanostructured lipid carriers (NLCs) to enhance apigenin (APG) efficacy as Nrf2 inhibitor, in concurrent administration with DTX in A549 NSCLC. The nanocarriers demonstrated several desirable properties like a narrow distributed nano-size (∼89 nm) and suitable encapsulation efficiency (∼70%). The successful cellular uptake was investigated via fluorescence microscopy and flow cytometry. The results of cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry revealed that HA-APG-NLCs had more cytotoxicity and synergistic effect combined with DTX. Moreover, evaluation of gene expression by real-time PCR showed that treatment of A549 cells with HA-APG-NLCs significantly caused a decreased Nrf2, MRP2, HO-1, Bcl-2, along with an increase in Bid mRNA levels compared to the other groups (p