ABSTRACT

Rare-earth-doped nanoparticles (NPs), such as NaGdF₄ nanocrystals doped with light-emitting rare earth ions, are promising bimodal probes that allow the integration of over 1000 nm near-infrared (OTN-NIR; NIR-II/III) fluorescence imaging and magnetic resonance imaging (MRI) of live bodies. A precise control of the particle size is the key factor for achieving a high signal-to-noise ratio in both NIR fluorescence and MR images and for regulating their function in the body. In this study, size-controlled NaGdF₄:Yb³⁺, Er³⁺ NPs prepared by stepwise crystal growth were used for in vivo bimodal imaging. Hexagonal NaGdF₄:Yb³⁺,Er³⁺ NPs coated with poly(ethylene glycol)-poly(acrylic acid) block copolymer, with hydrodynamic diameters of 15 and 45 nm, were prepared and evaluated as bimodal NPs for OTN-NIR fluorescence imaging and MRI. Their longitudinal (T₁) and transverse (T₂) relaxation rates at the static magnetic field strength of 1.0 T, as well as their cytotoxicity towards NIH3T3 cell lines, were evaluated and compared to study the effect of size. Using these particles, blood vessel visualization was achieved by MRI, with the highest relaxometric ratio (r₁/r₂) of 0.79 reported to date for NaGdF₄-based nanoprobes (r₁ = 19.78 mM⁻¹ s⁻¹), and by OTN-NIR fluorescence imaging. The results clearly demonstrate the potential of the size-controlled PEG-modified NaGdF₄:Yb³⁺,Er³⁺ NPs as powerful ‘positive’ T₁-weight contrast MRI agents and OTN-NIR fluorophores.

摘要

稀土掺杂的纳米颗粒（NPs），例如掺有发光稀土离子的NaGdF ₄纳米晶体，是有前途的双峰探针，可集成超过1000 nm的近红外（OTN-NIR; NIR-II / III）活体的荧光成像和磁共振成像（MRI）。精确控制粒径是在NIR荧光和MR图像中均实现高信噪比并调节其在体内功能的关键因素。在这项研究中，通过逐步晶体生长制备的尺寸受控的NaGdF ₄：Yb ³⁺，Er ³⁺ NP用于体内双峰成像。六角NaGdF ₄：Yb ³⁺，Er ³⁺制备了涂覆有水动力直径分别为15和45 nm的聚（乙二醇）-聚（丙烯酸）嵌段共聚物的NP，并将其评估为用于OTN-NIR荧光成像和MRI的双峰NP。评估并比较了它们在静态磁场强度为1.0 T时的纵向（T ₁）和横向（T ₂）弛豫率，以及它们对NIH3T3细胞系的细胞毒性，并比较了其对大小的影响。使用这些颗粒，可以通过MRI进行血管可视化，迄今为止，基于NaGdF ₄的纳米探针报道的最大弛豫比（r ₁ / r ₂）为0.79 （r ₁  = 19.78 mM ^-1s ^-1），并通过OTN-NIR荧光成像。结果清楚地证明了大小受控的PEG修饰的NaGdF ₄：Yb ³⁺，Er ³⁺ NPs作为强大的“阳性” T ₁重量对比MRI剂和OTN-NIR荧光团的潜力。