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.

Elnaz Salmani Javan,Davoud Jafari-Gharabaghlou,Hanieh Mousazadeh,Nosratollah Zarghami,Fatemeh Lotfi,Mehdi Dadashpour

doi:10.31557/apjcp.2022.23.2.519

Abstract

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.

Highlights

Cancer is an uncontrolled development of cells with the potential to attack, or spread to, other tissues and organs of the body (Jeddi et al, 2019; Nikmanesh et al, 2020; Abbasi et al, 2021)
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 poly lactic-coglycolic acid (PLGA)/polyethylene glycol (PEG)/ Fe3O4 NPs
Characterization of nanoparticles Spherical morphology homogeneously distributed without any significant aggregation in the synthesized NPs was confirmed via field emission scanning electron microscopy (FE-SEM) analysis

Summary

Introduction

Cancer is an uncontrolled development of cells with the potential to attack, or spread to, other tissues and organs of the body (Jeddi et al, 2019; Nikmanesh et al, 2020; Abbasi et al, 2021). Lung cancer is one of the most common and dangerous kinds of cancer throughout the world (Sheervalilou et al, 2016; Mellatyar et al, 2018). Lung cancer as a malignant tumor characterized through unchecked cell growth in the lung tissue (Adlravan et al, 2021). Different kinds of non-small cell lung cancer, are the mainly common types of lung cancer (Samadzadeh et al, 2021). Three standard therapeutic approaches of lung treatment options including surgery, chemotherapy and, radiation therapy usually are used according to the type and stage of cancer (Farajzadeh et al, 2018). Some phytochemicals such as Silibinin (Sil) and Metformin (Met) showed promising chemopreventive potential against different malignancies in both in vitro and in vivo studies (Chatran et al, 2018; Amirsaadat et al, 2021)

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Conclusion