Okubo Kyohei, Takeda Ryuta, Murayama Shuhei, Umezawa Masakazu, Kamimura Masao, Osada Kensuke, Aoki Ichio, Soga Kohei
Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan.
Group of Quantum-state Controlled MRI, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan.
Sci Technol Adv Mater. 2021 Mar 10;22(1):160-172. doi: 10.1080/14686996.2021.1887712.
Rare-earth-doped nanoparticles (NPs), such as NaGdF 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 NaGdF:Yb, Er NPs prepared by stepwise crystal growth were used for in vivo bimodal imaging. Hexagonal NaGdF:Yb,Er 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 ( ) and transverse ( ) 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 ( / ) of 0.79 reported to date for NaGdF-based nanoprobes ( = 19.78 mM s), and by OTN-NIR fluorescence imaging. The results clearly demonstrate the potential of the size-controlled PEG-modified NaGdF:Yb,Er NPs as powerful 'positive' -weight contrast MRI agents and OTN-NIR fluorophores.
稀土掺杂纳米颗粒（NPs），如掺杂发光稀土离子的NaGdF纳米晶体，是很有前景的双峰探针，可实现活体超过1000nm近红外（OTN-NIR；NIR-II/III）荧光成像和磁共振成像（MRI）。精确控制粒径是在近红外荧光和磁共振图像中实现高信噪比以及调节其在体内功能的关键因素。在本研究中，通过逐步晶体生长制备的尺寸可控的NaGdF:Yb,Er NPs用于体内双峰成像。制备了涂覆有聚（乙二醇）-聚（丙烯酸）嵌段共聚物、流体动力学直径为15和45nm的六方NaGdF:Yb,Er NPs，并将其作为用于OTN-NIR荧光成像和MRI的双峰纳米颗粒进行评估。评估并比较了它们在1.0T静磁场强度下的纵向（ ）和横向（ ）弛豫率，以及它们对NIH3T3细胞系的细胞毒性，以研究尺寸的影响。使用这些颗粒，通过MRI实现了血管可视化，基于NaGdF的纳米探针的弛豫率比值（ / ）高达0.79（ = 19.78 mM s），这是迄今为止报道的最高值，同时也通过OTN-NIR荧光成像实现了血管可视化。结果清楚地证明了尺寸可控的聚乙二醇修饰的NaGdF:Yb,Er NPs作为强大的“阳性” -权重对比MRI剂和OTN-NIR荧光团的潜力。
