Development of a Magnetic Nanostructure for Co-delivery of Metformin and Silibinin on Growth of Lung Cancer Cells: Possible Action Through Leptin Gene and its Receptor Regulation

Document Type : Research Articles


1 Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.

2 Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

3 Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran.

4 Department of Medical Biochemistry, Istanbul Aydin University, Istanbul, Turkey.


Objective: Chemotherapeutic combinational approaches would be more efficient in decreasing toxicity of drug, preventing tumor progression in relation to either drug alone. Hence, the aim of this study is to constract magnetic PLGA/PEG nanoparticles (NPs) co-loaded with Metformin (Met) and Silibinin (Sil) to investigate their cytotoxicity as well as their impact on  mRNA expression levels of leptin and leptin receptor genes in A549 lung cancer cells. Materials and Methods: The synthesized NPs were characterized by FTIR, FE-SEM, and VSM and then, MTT assay was utilized to assess and compare the cytotoxicity of various concentrations of the chemotheruptic molecules in pure and nanoformulated forms as well as in alone and combination state after 48 h exposure time. Moreover, the mRNA levels of leptin and its receptor genes expression were studied by quantitative real-time PCR. By co-encapsulation of Met and Sil into PLGA/PEG/ Fe3O4, cytotoxic efficiency of the compounds considerably augmented for all concentrations. Results: Cytotoxicity assay displayed that combination of Met and Sil had a synergistic concentration-dependent effect on A549 lung cancer cells. Moreover, qPCR data revealed that the expression levels of the leptin and leptin receptor was considerably reduced with increasing concentrations of drug-encapsulated magnetic NPs, especially Met/Sil-encapsulated PLGA/PEG/ Fe3O4 NPs. Conclusion: Present preliminary study shows that co-incorporating Met, Sil, Fe3O4 into PLGA/PEG NPs might provide a more promising and safe treatment strategy for lung cancer.


Main Subjects