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磁热疗诱导的可控细胞死亡:暴露时间、场强和纳米颗粒浓度的影响。

Controlled cell death by magnetic hyperthermia: effects of exposure time, field amplitude, and nanoparticle concentration.

机构信息

Instituto de Nanociencia de Aragón, University of Zaragoza, Mariano Esquillor, 50018 Zaragoza, Spain.

出版信息

Pharm Res. 2012 May;29(5):1319-27. doi: 10.1007/s11095-012-0710-z. Epub 2012 Feb 24.

DOI:10.1007/s11095-012-0710-z
PMID:22362408
Abstract

PURPOSE

To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death.

METHODS

Human-monocyte-derived DCs were co-incubated with dextran-coated MNPs. The cells were exposed to AMF (f = 260 kHz; 0 < H(0) < 12.7 kA/m) for intervals from 5 to 15 min. Morphology changes were assessed by scanning electron microscopy. Cell viability was measured by Trypan blue and fluorescence-activated cell sorting (FACS) using Annexin-propidium iodide markers.

RESULTS

We were able to control the DCs viability by a proper choice AMF amplitude and exposure time, depending on the amount of MNPs uploaded. About 20% of cells showed Annexin-negative/PI-positive staining after 5-10 min of AMF exposure.

CONCLUSIONS

Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the physical AMF parameters and MNPs concentration. Necrotic-like populations were observed after exposure times as short as 10 min, suggesting a fast underlying mechanism for cell death. Power absorption by the MNPs might locally disrupt endosomic membranes, thus provoking irreversible cell damage.

摘要

目的

研究交变磁场(AMF)对作为加热剂的负载磁性纳米颗粒(MNPs)的树突状细胞(DCs)死亡率的影响。筛选 AMF 暴露时间和幅度以及 MNPs 浓度,以评估受控场诱导细胞死亡的最佳条件。

方法

人单核细胞来源的 DCs 与葡聚糖包被的 MNPs 共孵育。将细胞暴露于 AMF(f = 260 kHz;0 < H(0) < 12.7 kA/m),暴露时间为 5 至 15 分钟。通过扫描电子显微镜评估形态变化。通过台盼蓝和使用 Annexin-propidium iodide 标记物的荧光激活细胞分选(FACS)测量细胞活力。

结果

我们能够通过适当选择 AMF 幅度和暴露时间,根据上传的 MNPs 量来控制 DCs 的活力。在 AMF 暴露 5-10 分钟后,约 20%的细胞表现出 Annexin 阴性/PI 阳性染色。

结论

通过适当调整物理 AMF 参数和 MNPs 浓度,可以获得负载 MNPs 的 DCs 的受控细胞死亡。仅在 10 分钟的暴露时间后即可观察到类似坏死的群体,表明细胞死亡存在快速的潜在机制。MNPs 的功率吸收可能会局部破坏内体膜,从而引发不可逆的细胞损伤。

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