It is a significant challenge to develop nanoscale magnetic resonance imaging (MRI) contrast agents with high performance of relaxation. In this work, Gd³⁺-doped CaF₂-based core–shell nanoparticles (CaF₂:Yb,Er@CaF₂:Gd) of sub-10 nm size were controllably synthesized by a facile sequential growth method. The as-prepared hydrophilic CaF₂:Yb,Er@CaF₂:Gd nanoparticles modified using PEG-PAA di-block copolymer benefited from the presence of Gd only in the outer CaF₂ layer of the nanoparticles, which exhibited r₁ as high as 21.86 mM⁻¹ s⁻¹ under 3.0 T, seven times as high as that of commercially used gadopentetate dimeglumine (Gd-DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion leakage phenomenon of the hydrophilic CaF₂:Yb,Er@CaF₂:Gd nanoparticles have been observed and confirmed. Clear vascular details can be observed in magnetic resonance angiography and obvious MR signal of 4T1 tumor area could be significantly improved by intravenous injection of the hydrophilic CaF₂:Yb,Er@CaF₂:Gd nanoparticles at a low dosage in mice. A series of in vivo biological safety evaluations confirmed the good biocompatibility of the hydrophilic CaF₂:Yb,Er@CaF₂:Gd nanoparticles, which might be employed in clinical blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.

中文翻译：

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CaF ₂：Yb，Er @ CaF ₂：Gd纳米粒子的顺序生长，用于有效的磁共振血管造影和肿瘤诊断

开发具有高松弛性能的纳米级磁共振成像（MRI）造影剂是一项重大挑战。在这项工作中，通过简便的连续生长方法可控制地合成了小于10 nm尺寸的Gd ³⁺掺杂的CaF ₂基核壳纳米粒子（CaF ₂：Yb，Er @ CaF ₂：Gd）。使用PEG-PAA二嵌段共聚物改性的亲水性CaF ₂：Yb，Er @ CaF ₂：Gd纳米颗粒仅在纳米颗粒的CaF ₂外层中存在Gd ，而r ₁高达21.86毫米^-1 s ^-1低于3.0 T，是市售的ado戊二酸二聚亮氨酸（Gd-DTPA）的7倍。已经观察到并确认了亲水性CaF ₂：Yb，Er @ CaF ₂：Gd纳米颗粒的低细胞毒性，无溶血现象和潜在的g离子泄漏现象。在磁共振血管造影中可以观察到清晰的血管细节，并且通过在小鼠中低剂量静脉内注射亲水性CaF ₂：Yb，Er @ CaF ₂：Gd纳米颗粒可以明显改善4T1肿瘤区域的明显MR信号。一系列体内生物安全性评估证实了亲水性CaF ₂：Yb，Er @ CaF ₂的良好生物相容性：Gd纳米颗粒，可作为安全有效的MRI探针用于临床血池成像和肿瘤诊断。