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磁性纳米颗粒联合甲氨蝶呤介导的磁热化疗治疗乳腺癌的体外研究

In vitro investigation on the magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate for breast cancer treatment.

作者信息

Zhao Lingyun, Huo Meijun, Liu Jiayi, Yao Zhu, Li Danye, Zhao Zhiwei, Tang Jintian

机构信息

Institute of Medical Physics and Engineering, Department of Engineering Physics, Key Laboratory of Particle and Radiation Imaging, Ministry of Education, Tsinghua University, Beijing 100084, China.

出版信息

J Nanosci Nanotechnol. 2013 Feb;13(2):741-5. doi: 10.1166/jnn.2013.6080.

DOI:10.1166/jnn.2013.6080
PMID:23646507
Abstract

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. In therapeutic oncology, hyperthermic adjuvant chemotherapy termed as thermochemotherapy plays an increasing role in multimodality cancer treatment. Currently, targeted nanothermotherapy is one of the effective hyperthermia approach based on magnetic nanoparticles (MNPs), which can be achieved by applying biocompatible nanoscaled metallic particles that convert electromagnetic energy into heat, for instance, magnetic fluid hyperthermia (MFH) mediated by superparamagnetic iron oxide nanoparticles (SPIONs). Upon exposure under alternative magnetic field (AMF), SPIONs can generate heat through oscillation of their magnetic moment. Nowadays, clinical trials at phase II are now under investigations for MFH on patients in Germany and Japan and demonstrate very inspiring for cancer therapy. In this work we explore the feasibility and effectiveness of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate, an anti-cancer drug, for breast cancer comprehensive treatment. Amino silane coated MNPs as agent of MFH were prepared by the chemical precipitation method. Physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under AMF. The in-vitro cytotoxicity results on human breast cancer cell MCF-7 by CCK-8 assay indicated the bi-modal cancer treatment approach for combined MFH and chemotherapy is more effective than mono-modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.

摘要

癌症综合治疗已得到充分认可,因为它能为对抗癌症提供一种有效的多模式方法。在肿瘤治疗学中,被称为热化疗的高温辅助化疗在多模式癌症治疗中发挥着越来越重要的作用。目前,靶向纳米热疗是基于磁性纳米颗粒(MNPs)的有效热疗方法之一,这可以通过应用将电磁能转化为热的生物相容性纳米级金属颗粒来实现,例如,由超顺磁性氧化铁纳米颗粒(SPIONs)介导的磁流体热疗(MFH)。在交变磁场(AMF)作用下,SPIONs可通过其磁矩振荡产生热量。如今,德国和日本正在对患者进行MFH的II期临床试验,结果令人鼓舞,对癌症治疗具有重要意义。在这项工作中,我们探索了磁性纳米颗粒与抗癌药物甲氨蝶呤联合介导的磁热化疗用于乳腺癌综合治疗的可行性和有效性。通过化学沉淀法制备了氨基硅烷包覆的MNPs作为MFH的试剂。通过各种仪器分析对MNPs进行了系统的理化表征。通过监测MNPs悬浮液在AMF下的温度升高来评估MNPs的感应加热性能。CCK-8法对人乳腺癌细胞MCF-7的体外细胞毒性结果表明,MFH与化疗联合的双模式癌症治疗方法比单模式治疗更有效,表明热疗对药物细胞毒性具有热增强作用。MNPs与甲氨蝶呤联合介导的磁热化疗可实现癌症综合治疗,因此在临床应用中具有巨大潜力。

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