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

机译:基于NaGdF4纳米粒子的分子探针用于体内腹膜内肿瘤异种移植的磁共振成像

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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 NaGdF4-PEG-mAb probes possessed satisfying tumor-specific targeting ability and strong MR contrast enhancement effects.
机译:通过高温方法合成了具有窄粒径分布的不同尺寸的NaGdF_4纳米晶体。配体交换后,通过使用同时带有磷酸酯和马来酰亚胺基团的不对称PEG将制备好的疏水性NaGdF_4纳米晶体转移到水中。进一步的研究表明,由PEG在同一侧带有两个磷酸基团的PEG包覆的水溶性NaGdF_4纳米晶体不仅在水和PBS缓冲液中表现出优异的胶体稳定性,而且比Gd-DTPA(Magnevist)具有更高的T1弛豫性。通过部分还原的抗EGFR单克隆抗体(mAb)上颗粒表面的马来酰亚胺残基与巯基之间的“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,通过使用磁共振(MR)成像技术检测裸鼠的腹膜内肿瘤异种移植物。结果表明,NaGdF4-PEG-mAb探针具有令人满意的肿瘤特异性靶向能力和强大的MR对比增强作用。

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