Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.
Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.
复制标题
交替的磁场诱导的热疗增加了血脑屏障模型中氧化铁纳米颗粒的关联/摄取和通量。
DOI：
10.1007/s11095-014-1561-6
复制
发表时间：
2015-05
影响因子：
3.7
通讯作者：
Yokel RA
中科院分区：
文献类型：
--
作者：
Dan M;Bae Y;Pittman TA;Yokel RA
超顺磁性氧化铁纳米颗粒（IONPs）正被研究用于脑癌治疗，因为交变磁场（AMF）激活它们产生热疗。对于中枢神经系统的应用，诊断和治疗药物的脑入口通常是必不可少的。我们假设amf诱导的热疗显著增加IONP血脑屏障（BBB）关联/摄取和通量。在室内合成了负载离子的交联纳米组件（cnna -IONPs）和传统的柠檬酸盐包覆离子（cit酸盐-IONPs）。采用两种血脑屏障Transwell®模型（bEnd）研究了CNA-IONP和柠檬酸盐- ionp血脑屏障细胞的结合/摄取和通量。3和MDCKII细胞)在常规和amf诱导的热疗暴露后。amf诱导的高温0.5 h没有改变CNA-IONP的大小，但加速了柠檬酸盐- ionp的聚集。amf诱导的0.5 h热疗增强了na - ionp和柠檬酸盐- ionp血脑屏障细胞的关联/摄取。在没有细胞死亡的情况下，与常规热疗和常温相比，它还增强了两种体外血脑屏障模型中CNA-IONPs的通量。在这些条件下没有观察到柠檬酸盐-离子离子通量。amf诱导的热疗也显著增强了细胞旁通路通量。这一机制似乎不仅仅涉及到na - ionps周围温度的升高。AMF激活na - ionps诱导的热疗有可能增加血脑屏障的通透性，用于各种脑部疾病的诊断和治疗。
Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood–brain barrier (BBB) association/uptake and flux. Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell® models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure. AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs. Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.