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基于 NaGdF4 纳米颗粒的分子探针用于体内腹腔肿瘤异种移植的磁共振成像。

NaGdF4 nanoparticle-based molecular probes for magnetic resonance imaging of intraperitoneal tumor xenografts in vivo.

机构信息

Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.

出版信息

ACS Nano. 2013 Jan 22;7(1):330-8. doi: 10.1021/nn304837c. Epub 2012 Dec 7.

Abstract

Differently sized NaGdF(4) nanocrystals with narrow particle size distributions were synthesized by a high temperature approach. Upon ligand exchange, the as-prepared hydrophobic NaGdF(4) nanocrystals were transferred into water by using asymmetric PEGs simultaneously bearing phosphate and maleimide groups. Further investigations demonstrated that the water-soluble NaGdF(4) nanocrystals, coated by PEG bearing two phosphate groups on the same side, exhibit not only excellent colloidal stability in water and PBS buffer, but also higher T1 relaxivity than Gd-DTPA (Magnevist). Through "click" reaction between the maleimide residue on particle surface and thiol group from the partly reduced anti-EGFR monoclonal antibody (mAb), NaGdF(4)-PEG-mAb nanoprobes were constructed, and their biocompatibility and binding specificity were evaluated through in vitro experiments. A series of in vivo experiments were then carried out for detecting intraperitoneal tumor xenografts in nude mice by using magnetic resonance (MR) imaging technique. The results revealed that the NaGdF(4)-PEG-mAb probes possessed satisfying tumor-specific targeting ability and strong MR contrast enhancement effects.

摘要

不同尺寸、粒径分布较窄的 NaGdF(4)纳米晶通过高温法合成。通过配体交换,将制备的疏水性 NaGdF(4)纳米晶用同时带有磷酸酯和马来酰亚胺基团的不对称 PEG 转化为水相。进一步的研究表明,由同一侧带有两个磷酸酯基团的 PEG 包覆的水溶性 NaGdF(4)纳米晶不仅在水中和 PBS 缓冲液中具有优异的胶体稳定性,而且 T1 弛豫率也高于 Gd-DTPA(Magnevist)。通过纳米晶表面的马来酰亚胺残基与部分还原的抗 EGFR 单克隆抗体(mAb)的巯基之间的“点击”反应,构建了 NaGdF(4)-PEG-mAb 纳米探针,并通过体外实验评估了它们的生物相容性和结合特异性。然后进行了一系列体内实验,通过磁共振(MR)成像技术检测裸鼠腹腔内肿瘤异种移植。结果表明,NaGdF(4)-PEG-mAb 探针具有令人满意的肿瘤特异性靶向能力和较强的磁共振对比增强效果。

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