iMdea Nanociencia , Campus Universitario de Cantoblanco, C\Faraday, 9 , 28049 Madrid , Spain.
Institute for Science and Technology in Medicine , Keele University , Guy Hilton Research Centre, Thornburrow Drive , Hartshill, Stoke-on-Trent ST4 7QB , United Kingdom.
ACS Nano. 2018 Mar 27;12(3):2741-2752. doi: 10.1021/acsnano.7b08995. Epub 2018 Mar 9.
Magnetic nanoparticles exposed to alternating magnetic fields have shown a great potential acting as magnetic hyperthermia mediators for cancer treatment. However, a dramatic and unexplained reduction of the nanoparticle magnetic heating efficiency has been evidenced when nanoparticles are located inside cells or tissues. Recent studies suggest the enhancement of nanoparticle clustering and/or immobilization after interaction with cells as possible causes, although a quantitative description of the influence of biological matrices on the magnetic response of magnetic nanoparticles under AC magnetic fields is still lacking. Here, we studied the effect of cell internalization on the dynamical magnetic response of iron oxide nanoparticles (IONPs). AC magnetometry and magnetic susceptibility measurements of two magnetic core sizes (11 and 21 nm) underscored differences in the dynamical magnetic response following cell uptake with effects more pronounced for larger sizes. Two methodologies have been employed for experimentally determining the magnetic heat losses of magnetic nanoparticles inside live cells without risking their viability as well as the suitability of magnetic nanostructures for in vitro hyperthermia studies. Our experimental results-supported by theoretical calculations-reveal that the enhancement of intracellular IONP clustering mainly drives the cell internalization effects rather than intracellular IONP immobilization. Understanding the effects related to the nanoparticle transit into live cells on their magnetic response will allow the design of nanostructures containing magnetic nanoparticles whose dynamical magnetic response will remain invariable in any biological environments, allowing sustained and predictable in vivo heating efficiency.
暴露于交变磁场中的磁性纳米粒子在作为癌症治疗的磁热疗介质方面显示出巨大的潜力。然而，当纳米粒子位于细胞或组织内部时，其纳米粒子磁加热效率会出现明显且无法解释的降低。最近的研究表明，与细胞相互作用后纳米粒子的团聚和/或固定化增强是可能的原因，尽管缺乏对生物基质对交流磁场中磁性纳米粒子磁响应影响的定量描述。在这里，我们研究了细胞内化对氧化铁纳米粒子（IONP）动态磁响应的影响。两种磁芯尺寸（11nm 和 21nm）的交流磁强计和磁化率测量强调了细胞摄取后动态磁响应的差异，较大尺寸的影响更为明显。我们采用了两种方法来实验确定活细胞内磁性纳米粒子的磁热损失，而不会危及它们的活力以及磁性纳米结构用于体外热疗研究的适用性。我们的实验结果——得到了理论计算的支持——表明，细胞内 IONP 团聚的增强主要驱动细胞内化效应，而不是细胞内 IONP 的固定化。了解与纳米粒子进入活细胞相关的效应及其对磁响应的影响，将允许设计包含磁性纳米粒子的纳米结构，其动态磁响应在任何生物环境中都保持不变，从而实现持续和可预测的体内加热效率。
