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.

中文翻译：

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MFP-FePt-GO 纳米复合材料通过激活线粒体介导的细胞凋亡和损害 DNA 损伤修复来促进非小细胞肺癌的放射敏感性。

背景：纳米医学的最新进展为肿瘤治疗提供了有希望的替代方案，以提高癌症患者的生存率和生活质量。本研究旨在探索新型纳米复合材料 (NCs) MFP-FePt-GO 对非小细胞肺癌 (NSCLC) 的抗肿瘤作用的洞察机制。方法：将化学共还原方法应用于MFP-FePt-GO NCs的合成过程。用光谱仪和透射电子显微镜测量了 NCs 的化学合成效率和形貌。进行集落形成试验和细胞凋亡以评估 NCs 对辐射的放射敏感性影响。然后，我们通过流式细胞术检测细胞线粒体膜电位和活性氧 (ROS) 水平，以进一步探索细胞死亡的原因。进行免疫荧光染色和共聚焦以确定 DNA 损伤修复。刘易斯肺癌动物模型用于测量体内安全性和抗肿瘤效率。结果：合成并功能化了基于层状结构磁性氧化石墨烯和聚乙二醇药物递送系统设计的新型 NCs MFP-FePt-GO，用于甲硝唑和 5-氟尿嘧啶的共同递送。虽然没有观察到严重的过敏、肝肾损伤或与药物相关的死亡，但 MFP-FePt-GO NCs 在体内和体外都促进了 NSCLC 细胞的放射敏感性。它通过激活内在线粒体介导的细胞凋亡和损害 DNA 损伤修复来改善辐射的影响。这种 NCs 还诱导了 ROS 爆发，从而抑制了抗氧化蛋白的表达并诱导了细胞凋亡。此外，MFP-FePt-GO NCs 阻止了 NSCLC 细胞的迁移和侵袭。结论：MFP-FePt-GO NCs与放射协同抗肿瘤作用，消除肿瘤。由于具有良好的安全性和有效性，这种新型 NCs 可能成为 NSCLC 患者的潜在放射敏感剂。