The effect of Gd-DOTA locations within PLGA-b-PEG micelles encapsulated IR-1061 on bimodal over-1000 nm near-infrared fluorescence and magnetic resonance imaging
The effect of Gd-DOTA locations within PLGA-b-PEG micelles encapsulated IR-1061 on bimodal over-1000 nm near-infrared fluorescence and magnetic resonance imaging
复制标题
封装 IR-1061 的 PLGA-b-PEG 胶束内 Gd-DOTA 位置对双峰超过 1000 nm 近红外荧光和磁共振成像的影响
DOI：
10.1039/d2bm01213h
复制
发表时间：
2022
影响因子：
6.6
通讯作者：
K. Soga
中科院分区：
文献类型：
--
作者：
7.T.K.D. Doan;M. Umezawa;K. Okubo;M. Kamimura;M. Yamaguchi;H. Fujii;K. Soga
多模态成像在生物医学研究中很有吸引力，因为它可以提供单个技术无法实现的物体的多维信息。特别是，将超过一千纳米的近红外（OTN-NIR）荧光和磁共振（MR）成像相结合，有望以高灵敏度和结构信息检测病变。在此，我们描述了一种双峰OTN-NIR/MRI探针的发展钆-四氮杂环十二烷四乙酸（Gd-DOTA）共轭聚（乳酸-共-乙醇酸）-嵌段-聚（乙二醇）共聚物（PLGA-b-PEG）胶束封装IR-1061在两个不同的位置。一种构型在亲水性壳的PEG末端含有Gd-DOTA，另一种构型在PLGA/PEG的边界含有Gd-DOTA。两种结构在生物环境中的荧光和R1弛豫速率显示出显著差异;在PLGA/PEG边界处具有Gd-DOTA的结构在活小鼠中表现出稳定的荧光和T1信号分布。Gd-DOTA与PEG的引入比例对于控制两种结构的性质是重要的;更高的Gd-DOTA比例对于对比度增强效果是优选的。我们发现，当Gd-DOTA结合到PEG末端时，Gd-DOTA比率高于10%会降低荧光强度。相比之下，在PLGA/PEG的边界处引入70% Gd-DOTA没有表现出降低的信号，并且结构稳定性随着Gd-DOTA的比例增加而增强。总之，我们证实了Gd-DOTA的位置是设计高性能探针的关键因素。当Gd-DOTA设置在PLGA/PEG的边界上时，整体性能得到改善。通过控制探针结构来改善这些性质，对于未来的生物医学应用是有希望的。
Multimodal imaging is attractive in biomedical research because it can provide multidimensional information about objects that individual techniques cannot accomplish. In particular, combining over one-thousand-nanometer near-infrared (OTN-NIR) fluorescence and magnetic resonance (MR) imaging is promising for detecting lesions with high sensitivity and structural information. Herein, we describe the development of a bimodal OTN-NIR/MRI probe from gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) conjugated poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer (PLGA-b-PEG) micelle encapsulated IR-1061 at two different locations. One configuration contains Gd-DOTA at the end of the PEG of the hydrophilic shell and the other contains Gd-DOTA at the border of PLGA/PEG. The two structures show remarkable differences in fluorescence and R1 relaxation rates in biological environments; the structure with Gd-DOTA at the border of PLGA/PEG exhibits stable fluorescence and T1 signal distribution in live mice. The introduction ratio of Gd-DOTA to PEG is significant for controlling the properties of both structures; a higher Gd-DOTA ratio is preferable for the contrast enhancement effect. We found that Gd-DOTA ratios higher than 10% degraded the fluorescence intensity when Gd-DOTA was bound to the end of PEG. In contrast, the introduction of 70% Gd-DOTA at the border of PLGA/PEG did not exhibit a degraded signal, and the structural stability was enhanced with higher ratios of Gd-DOTA. In conclusion, we confirmed that the location of Gd-DOTA is a crucial factor in designing high-performance probes. The overall properties improve when Gd-DOTA is set on the border of PLGA/PEG. These improvements in the properties by controlling the probe structures are promising for future biomedical applications.