IOSR Journal Of Pharmacy And Biological Sciences (IOSR-JPBS) e-ISSN:2278-3008, p-ISSN:2319-7676. Volume 16, Issue 4 Ser. III (Jul. – Aug. 2021), PP 37-46 www.Iosrjournals.Org DOI: 10.9790/3008-1604033746 www.iosrjournals.org 37 | Page Molecular studies on the therapeutic effects of Mn-Zn- Fe 2 O 4 /Se nanocomposite for hyperthermia treatment on liver cancer Huda Y. Gedawy 1,2 , Hemely A. Hassan 1 , A. A. Ebnalwaled 2,3* , Nadia S. Mahrous 1 1 Zoology Department, Faculty of Science, South Valley University, 83523, Qena, Egypt. 2 Electronics and Nano Devices Lab, Physics Department, Faculty of Science South Valley University, Qena, 83523 Egypt 3 Faculty of Nanotechnology for Postgraduate Studies, Cairo University, Sheikh Zayed Campus, 6 th October City, Giza, 12588, Egypt Abstract In this paper, we studied the effect of Mn-Zn-Fe 2 O 4 /Se nanocomposite which was synthesized by coprecipitation method and investigated its therapeutic effect that induced by an alternating magnetic field on xenograft liver cancer in mice. Mn-Zn-Fe 2 O 4 /Se was described by X - ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). We also studied cytotoxicity of Mn-Zn-Fe 2 O 4 /Se nanocomposite on the HepG2 cell line. The cytotoxicity results revealed high toxicity against HepG2 cells for higher concentrations (>250 μg/mL) of Mn-Zn-Fe 2 O 4 /Se but were found to be non-toxic at lower concentrations. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate gene expression of caspase 3, Bcl-2 and p53. The results were showed that the expression level of P53 and Casp3 was clearly up-regulated, while the expression level of Bcl-2 was down-regulated (P<0.05) after hyperthermia in treated groups. Keywords: Mn-Zn-Fe 2 O 4 /Se nanocomposite; cytotoxicity; RT-PCR. --------------------------------------------------------------------------------------------------------------------------------------- Date of Submission: 25-08-2021 Date of Acceptance: 09-09-2021 --------------------------------------------------------------------------------------------------------------------------------------- I. Introduction Liver cancer is the fourth major cause of cancer-related death worldwide, and according to the estimations of the World Health Organization, more than one million people will be fatal from this disease in 2030. Liver cancer represents a global health challenge, and its incidence is increasing worldwide (Villanueva, 2019). It is supposed that, by 2025, more than 1 million individuals will be influenced by liver cancer every year (Llovet et al., 2021). Major risk factors for liver cancer involve hepatitis viral infection, additives of food, alcohol, aflatoxins, environmental and industrial toxic chemicals, water and air pollutants (Jemal et al., 2007). Liver cancer is also emerging due to inflammation that increase deoxyribonucleic acid (DNA) damage and chromosomal abnormalities (Buitrago-Molina et al., 2013), It is known that both genomic instability and genetic alteration are a popular features of human liver cancer. Surgical resection has been known as the most effective method for the treatment of liver cancer (Parks and Garden, 2001), but it is only showed for a small number of liver cancer patients. Radiotherapy and chemotherapy have been widely used in tumor regions but leading to fatal effects on healthy tissues (Hildebrandt et al., 2002). Although these ways can increase the intracellular temperature up to cancer cell death, they will also inflict damage at healthy tissues (Ferrari, 2005). So, it is necessary to search for a new method to treat liver cancer. Magnetic fluid hyperthermia (MFH) opens a new trend for cancer treatments. Latterly, utilizing of magnetic nanoparticles (MNPs) in medical applications (e.g., magnetic fluid hyperthermia (MFH), magnetic resonance imaging and magnetic gene transfection) have had an upward trend. Hyperthermia with MNPs is a hopeful modality in the treatment of cancer. The basis of this technique is to damage cancer cells by heating them up without fatal effects on normal tissues (Doaga et al., 2013). In comparison with other treatment techniques, this technique is a physical therapy with little side effects, and it can be accompanied by other therapies like chemotherapy and radiotherapy to realize resistant malignant cells to these therapies (Sun et al., 2013) and (Heidari et al., 2016). MFH was firstly suggested in 1957 by (Gilchrist et al., 1957) to damage cancer in lymph nodes by inoculated them with ‘particulate matter’ of maghemite and applying an alternating magnetic field (AMF) to stimulate ‘selective inductive heating’.