Int J Biol Sci 2020; 16(12):2145-2158. doi:10.7150/ijbs.46194

Research Paper

MFP-FePt-GO Nanocomposites Promote Radiosensitivity of Non-Small Cell Lung Cancer Via Activating Mitochondrial-Mediated Apoptosis and Impairing DNA Damage Repair

Shan Peng1, Yingming Sun1, Yuan Luo1, Shijing Ma1, Wenjie Sun1, Guiliang Tang1, Shuying Li1, Nannan Zhang1, Jiangbo Ren2, Yu Xiao2, Xuefeng Liu3, Junhong Zhang1,4,5, Yan Gong2,✉, Conghua Xie1,4,5,✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
2. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
3. Department of Pathology, Lombardi Comprehensive Cancer Center Georgetown University Medical School, Washington DC, USA
4. Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China
5. Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China

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Citation:
Peng S, Sun Y, Luo Y, Ma S, Sun W, Tang G, Li S, Zhang N, Ren J, Xiao Y, Liu X, Zhang J, Gong Y, Xie C. MFP-FePt-GO Nanocomposites Promote Radiosensitivity of Non-Small Cell Lung Cancer Via Activating Mitochondrial-Mediated Apoptosis and Impairing DNA Damage Repair. Int J Biol Sci 2020; 16(12):2145-2158. doi:10.7150/ijbs.46194. Available from http://www.ijbs.com/v16p2145.htm

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Abstract

Background: Recent advances in nanomedicine provided promising alternatives for tumor treatment to improve the survival and life quality of cancer patients. This study was designed to explore the insight mechanisms of the anti-tumor effects of the novel nanocomposites (NCs) MFP-FePt-GO with non-small cell lung cancer (NSCLC).

Methods: A chemical co-reduction method was applied to the synthesis process of MFP-FePt-GO NCs. The chemical synthesis efficiency and morphology of the NCs were measured with spectroscope and transmission electron microscope. Colony formation assay and cell apoptosis were conducted to assess the radiosensitivity effect of NCs with radiation. Then, we detected cell mitochondrial membrane potential and reactive oxygen species (ROS) level by flow cytometry to further explore the cause of cell death. Immunofluorescence staining and Confocal were carried out to determine the DNA damage repair. A Lewis lung carcinoma animal model was used to measure safety and anti-tumor efficiency in vivo.

Results: The novel NCs MFP-FePt-GO designed on a lamellar-structure magnetic graphene oxide and polyethylene glycol drug delivery system was synthesized and functionalized for co-delivery of metronidazole and 5-fluorouracil. While no severe allergies, liver and kidney damage, or drug-related deaths were observed, MFP-FePt-GO NCs promoted radiosensitivity of NSCLC cells both in vivo and in vitro. It improved the effects of radiation via activating intrinsic mitochondrial-mediated apoptosis and impairing DNA damage repair. This NCs also induced a ROS burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, MFP-FePt-GO NCs prevented NSCLC cell migration and invasion.

Conclusion: MFP-FePt-GO NCs showed a synergistic anti-tumor effect with radiation to eliminate tumors. With good safety and efficacy, this novel NCs could be a potential radiosensitive agent for NSCLC patients.

Keywords: MFP-FePt-GO nanocomposites, radiosensitivity, non-small cell lung cancer, apoptosis, DNA damage repair