Design and fabrication of a dual-drug loaded nano-platform for synergistic anticancer and cytotoxicity effects on the expression of leptin in lung cancer treatment

Abstract

Lung cancer is progressive and fatal malignancy and is one of the main causes of cancer-related death worldwide. Leptin (LEP) is a cytokine derived from adipocyte that is known to be a key mitogenic agent in lung carcinogenesis. Excessive amounts of systemic and pulmonary LEP are contributed with an enhanced risk of lung cancer. Currently, combinatorial treatments in cancer therapy are of intense interest. Metformin (Met) and Curcumin (Cur) are bioactive compounds that have several anti-cancer properties in pre-clinical and clinical studies. Herein, a dual-drug loaded nano-platform was designed for targeted drug delivery to A549 lung carcinoma cells. Met/Cur-loaded poly (D, L lactide-co-glycolide)-b-poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs) were synthesized. The inhibitory property of dual drug-loaded PLGA/PEG NPs on LEP and LEP receptor genes expression was determined compared to Met and Cur. DLS, FTIR, XRD, SEM and TEM techniques were employed for the characterization of synthesized NPs as well as nano-formulated drugs. The pattern of in-vitro drugs released from PLGA-PEG NPs was investigated through dialysis method. Cytotoxicity effects of free, nanocapsulated, and dual-loaded drugs on A549 cells were assessed by MTT assay. In addition, the expression of LEP and LEP receptor genes in A549 cells after treatments were evaluated through real-time PCR assay. According to the results, free and nanocapsulated forms of Cur and Met exhibited a cytotoxic effect on A549 cells in a dose-dependent pattern. In particular, Met-Cur-PLGA/PEG NPs posse synergistic anti-cancer properties than free and nanocapsulated forms of the drugs. Likewise, expression of LEP and LEP receptor genes in Met-Cur-PLGA/PEG NPs treated cells was much more suppressed compared to cells, which were incubated with free and nanocapsulated forms of the drugs. Our findings suggested that the co-capsulation of Met and Cur in PLGA/PEG NPs could significantly increase the efficiency of targeted drug delivery for cancer treatment proposes.