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PMMA-Fe3O4 for internal mechanical support and magnetic thermal ablation of bone tumors.
Theranostics ( IF 12.4 ) Pub Date : 2019-01-01 , DOI: 10.7150/thno.34157
Kexiao Yu 1, 2 , Bing Liang 2 , Yuanyi Zheng 3 , Agata Exner 4 , Michael Kolios 5 , Tiantian Xu 6 , Dajing Guo 7 , Xiaojun Cai 3 , Zhigang Wang 2 , Haitao Ran 2 , Lei Chu 1 , Zhongliang Deng 1
Affiliation  

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works. Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe3O4 nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro. Results: An NP content of 6% Fe3O4 (PMMA-6% Fe3O4, mFe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe3O4 implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels. Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe3O4 NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.

中文翻译:

PMMA-Fe3O4用于骨肿瘤的内部机械支持和磁热消融。

背景:在骨肿瘤治疗领域中,微创治疗方式引起了人们的极大兴趣。然而,在临床工作中,提供可靠的机械支持和快速杀死肿瘤细胞以实现身体功能的快速恢复仍然是挑战。方法:由分布在聚甲基丙烯酸甲酯(PMMA)骨水泥中的Fe3O4纳米粒子(NPs)开发出一种具有两种功能的材料,即机械支撑和磁热消融。系统地并成功地在体外和离体评估了磁场诱导的热消融的机械性能和效率。CT图像和病理检查已成功应用于评估兔骨肿瘤模型的治疗效果。在体内对兔子进行生物安全性评估,并在体外进行细胞毒性测试。结果:6%Fe3O4的NP含量(PMMA-6%Fe3O4,mFe:0.01 g)为体内研究提供了最合适的性能。治疗后56天的随访中,骨肿瘤被消融,没有明显的副作用。CT图像中的病理检查和新的骨形成清楚地表明,骨肿瘤已被完全消除。相应地,治疗后,骨肿瘤转移的趋势明显降低。此外,PMMA-6%Fe3O4植入物具有精心设计的机械性能,使荷瘤兔腿具有极佳的仿生骨骼结构和内部支撑。生物安全性评估未引起免疫反应的增加或减少,并且主要功能参数均处于正常水平。结论:我们提出了一本小说,基于含Fe3O4 NPs的PMMA的磁热消融的高效,微创方法,可以完成骨肿瘤的完全消退和骨缺损的修复;这种方法在暴露于交变磁场(AMF)后显示出对兔VX2胫骨平台肿瘤消融的出色加热能力,并为骨骼修复提供了机械支持。这种新型且功能强大的双重功能植入物是一种有前途的微创治疗骨肿瘤的药物,具有良好的临床翻译潜力。
更新日期:2019-01-01
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