Iron oxide particles covered with hexapeptides targeted at phosphatidylserine as MR biomarkers of tumor cell death
Iron oxide particles covered with hexapeptides targeted at phosphatidylserine as MR biomarkers of tumor cell death
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DOI：
10.1002/cmmi.382
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发表时间：
2010-09-01
影响因子：
--
通讯作者：
Gallez, B.
中科院分区：
文献类型：
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作者：
Radermacher, K. A.;Boutry, S.;Gallez, B.
这项研究的目的是评估一种新的磁共振造影剂检测细胞死亡的能力，作为抗癌治疗疗效的生物标志物。磷脂酰丝氨酸靶向六肽（E3）与聚乙二醇化的超小氧化铁纳米颗粒（USPIO）偶联，可以通过磁共振成像（MRI）和电子顺磁共振（EPR）检测。通过x波段EPR评估，USPIO与staurosporine处理的TLT（可移植肝肿瘤）细胞的结合表明，与USPIO与重组肽或未移植的USPIO相比，移植了E3肽的USPIO结合的程度是移植了E3肽的USPIO的两倍。活体实验采用TLT细胞肌内植入NMRI小鼠，辐照诱导肿瘤细胞死亡。静脉注射不同类型的USPIO后，分别用体外x波段EPR、体内l波段EPR和t -2加权MRI评估造影剂的积累情况。在受辐照的肿瘤中，与对照颗粒或未治疗组织中的目标颗粒相比，靶向USPIO颗粒的积累更多。综上所述，以磷脂酰丝氨酸为靶点的USPIO颗粒可以检测到死亡组织。这种分子靶向系统应该作为肿瘤治疗反应的潜在生物标志物进一步进行评估。版权所有John Wiley & Sons， Ltd。
The aim of the study was to evaluate the ability of a new MR contrast agent to detect cell death as a biomarker of the efficacy of anti-cancer treatment. The phosphatidylserine-targeted hexapeptide (E3) was coupled to pegylated ultrasmall iron oxide nanoparticles (USPIO) that can be detected by magnetic resonance imaging (MRI) and by electron paramagnetic resonance (EPR). USPIO binding to staurosporine-treated TLT (transplantable liver tumor) cells, evaluated by X-Band EPR, indicated twice as much binding of USPIO grafted with the E3 peptide, compared with USPIO grafted with a scrambled peptide or ungrafted USPIO. In vivo experiments were carried out using TLT cells implanted intramuscularly into NMRI mice, and tumor cell death was induced by irradiation. After intravenous injection of the different types of USPIO, the accumulation of contrast agent was evaluated ex vivo by X-band EPR, in vivo by L-band EPR and by T-2-weighted MRI. In irradiated tumors there was greater accumulation of the targeted USPIO particles compared with control particles or compared with the targeted particles in untreated tissues. In conclusion, phosphatidylserine-targeting of USPIO particles can detect dying tissues. This molecular targeted system should be evaluated further as a potential biomarker of tumor response to treatment. Copyright (C) 2010 John Wiley & Sons, Ltd.