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Haohan Zhou,1,2,* Jiayi Tian,3,* Hongyu Sun,1 Jiaying Fu,1 Nan Lin,1 Danni Yuan,1 Li Zhou,3 Meihui Xia,3 Liankun Sun1 1Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200000, People’s Republic of China; 3First Hospital, Jilin University, Changchun, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liankun Sun, Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China, Email sunlk@jlu.edu.cn Meihui Xia, First Hospital, Jilin University, Changchun, 130021, People’s Republic of China, Email xiamh@jlu.edu.cnPurpose: Magnetic iron oxide nanoparticle (MNP) drug delivery system is a novel promising therapeutic option for cancer treatment. Material issues such as fabrication and functionalized modification have been investigated; however, pharmacologic mechanisms of bare MNPs inside cancer cells remain obscure. This study aimed to explore a systems pharmacology approach to understand the reaction of the whole cell to MNPs and suggest drug selection in MNP delivery systems to exert synergetic or additive anti-cancer effects.Methods: HeLa and SiHa cell lines were used to estimate the properties of bare MNPs in cervical cancer through 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and enzyme activity assays and cellular fluorescence imaging. A systems pharmacology approach was utilized by combining bioinformatics data mining with clinical data analysis and without a predefined hypothesis. Key genes of the MNP onco-pharmacologic mechanism in cervical cancer were identified and further validated through transcriptome

Yunhan Zhang,1,* Meihui Xia,2,* Zizhen Zhou,3 Xiaoqing Hu,1 Jiabin Wang,1 Meiyu Zhang,3 Yi Li,4 Liankun Sun,1 Fangfang Chen,4,5 Huimei Yu1,6 1Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China; 2Department of Obstetrics & Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 3Clinical Medical College, Jilin University, Changchun 130021, People’s Republic of China; 4State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, Jilin 130012, People’s Republic of China; 5Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 6Animal Experiment Center, College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huimei YuKey Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaTel +86 431 85619485Email yuhuimei@jlu.edu.cnFangfang ChenDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 431 84995312Email cff@jlu.edu.cnMethods: In this study, we used MTT assays to demonstrate that a combination of SPIO-Serum and wild-type p53 overexpression can reduce ovarian cancer cell viability in vitro. Prussian blue staining and iron assays were used to determine changes in intracellular iron concentration following SPIO-Serum treatment. TEM was used to evaluate any mitochondrial damage induced by SPIO-Serum treatment