Evaluation of the effect of magnetic nanoparticles loaded ۵_fluorouracil (۵-FU) on colon cell line LS۱۷۴T

۱.Background Large intestine cancer, also known as colon cancer or rectal cancer, is the growth of cancer cells in the colon or rectum. Among cancers, this cancer is the third most common cause of death, and among Iranian men and women, this cancer is ranked fourth and is the second most common cancer, respectively (۱). The risk factors that cause colon cancer are mainly caused by lifestyle and adverse environmental factors, such as improper diet, alcohol consumption, obesity, smoking, and lack of physical activity, and a small number of cases are caused by hereditary genetic factors (۱-۳). Common methods of cancer treatment, such as surgery, radiation therapy, and chemotherapy, and new methods of cancer treatment, which include gene therapy, immunotherapy, targeted therapy, alternative therapy, the use of cell therapy, hormone therapy, and nanotechnology, are used to treat this cancer (۴, ۵). The aim of this study was to use multiple components, including drug-loaded NPs, to determine cytotoxicity and apoptotic gene expression in colon cancer cells. ۲. Objectives ۵-Fluorouracil or ۵-FU (Adrucil) is a cytotoxic chemotherapy drug. It causes cytotoxicity by interfering with essential biosynthetic activities by inhibiting the action of the thymidylate synthase enzyme or by miscombining its metabolites during ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis. Among magnetic NPs that can be used as drug carriers in medical science, iron oxide NPs are the better choice due to the fact that transferring the drug to the targeted organ can decrease medication dosage and drug side effects (۷). The purpose of this study was to investigate the anticancer effect of the combination of NP with ۵-FU loaded on it on the cell survival of colon cancer cell line LS۱۷۴T (۸). ۳. Methods ۳.۱. Synthesis of Fe۳O۴ The facile precipitation method was used for synthesizing metallic nanoparticles. ۳.۲. Synthesis of Graphene Quantum Dots (GQDs) ۳.۳. Preparation of Fe۳O۴/GQDs Nanohybrid ۳.۴. Preparation of Cu-(BDC)/Fe۳O۴/GQDs ۳.۵. Drug Loading Studies ۳.۶. Cell Culture ۳.۷. MTT Test ۳.۸. mRNA Extraction ۳.۹ . Reverse Transcription Polymerase Chain Reaction ۳.۱۰. Real-Time Polymerase Chain Reaction ۳.۱۱. Statistical Analysis:GraphPad Prism ۹ was used to draw graphs and analyze the data. ۴. Results ۴.۱. Characterization of Synthesized Nanocomposite The nanocomposites exhibit cubic crystalline frameworks of Cu(BDC) with spherical particles related to the presence of Fe۳O۴/GQDs nanohybrids (۸, ۹). The crystalline structure of Cu(BDC)/Fe۳O۴/GQDs was examined through powder XRD analysis . The magnetization curve of Cu(BDC)/Fe۳O۴/GQDs was obtained using the VSM technique at room temperature . It showed an S-like curve with about ۱۱.۵ emu/g magnetization. This amount of magnetization could transfer drug nanocarrier to a target site using an external magnetic field, which is beneficial in biomedical sciences. ۵-FU was loaded into the Cu(BDC)/Fe۳O۴/GQDs nanocomposite by immersing it into the drug solution. The loading capacity of ۵-FU was measured to be ۹۰.۳ ± ۰.۵% using UV-vis spectroscopy at ۲۶۶ nm. ۴.۲. Quantitative Polymerase Chain Reaction Results In general, the results showed the induction of apoptosis by nano-drug through increasing the expression of BAX and BAD and decreasing the expression of the BCL-۲.

کلیدواژه ها:

Toxicity Test ، Magnetic Nanoparticles ، Apoptosis