用于核磁共振成像分析的 pH 响应型 i-motif-共轭纳米粒子

IF 3.5 Q2 CHEMISTRY, ANALYTICAL
Kristine Y. Ma, Mireia Perera-Gonzalez, Nicole I. Langlois, Owen M. Alzubi, Joseph D. Guimond, Chris A. Flask and Heather A. Clark
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引用次数: 0

摘要

钆(Gd)基造影剂(CA)被广泛用于增强磁共振成像(MRI)中的解剖细节。通过调节信号来成像和监测生化过程(如 pH 值),大量研究已将造影剂领域扩展到生物响应造影剂。在这项工作中,我们介绍了基于 DNA 的纳米结构的模块化动态致动机制,这是一种基于旋转相关时间 τR 来调节 MRI 信号的新方法。我们将 pH 响应寡核苷酸(i-motif)和临床标准 CA(Gd-DOTA)相结合,开发出了 pH 响应 MRI CA。i-motif 在酸性条件下会折叠成一个四重链,与金纳米粒子(iM-GNP)结合后,其弛豫度 r1 比未结合的 i-motif 有所提高。在体外,iM-GNP 使 r1 在 pH 值递减范围(7.5 - 4.5)内显著增加,计算 pKa = 5.88 ± 0.01,每 0.1 pH 单位变化 16.7%。相比之下,使用无反应 DNA 链(T33-GNP)的对照 CA 在相同的 pH 值范围内 r1 没有显著变化。在 20% 的人血清中对 iM-GNP 进行了进一步评估,结果显示,从中性 pH 值到酸性 pH 值,信号增加了 28.14 ± 11.2%。这种方法为τR调制的生物响应性磁共振成像CAs的新型可编程动态DNA基复合物铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

pH-responsive i-motif-conjugated nanoparticles for MRI analysis†

pH-responsive i-motif-conjugated nanoparticles for MRI analysis†

Gadolinium (Gd)-based contrast agents (CAs) are widely used to enhance anatomical details in magnetic resonance imaging (MRI). Significant research has expanded the field of CAs into bioresponsive CAs by modulating the signal to image and monitor biochemical processes, such as pH. In this work, we introduce the modular, dynamic actuation mechanism of DNA-based nanostructures as a new way to modulate the MRI signal based on the rotational correlation time, τR. We combined a pH-responsive oligonucleotide (i-motif) and a clinical standard CA (Gd-DOTA) to develop a pH-responsive MRI CA. The i-motif folds into a quadruplex under acidic conditions and was incorporated onto gold nanoparticles (iM-GNP) to achieve increased relaxivity, r1, compared to the unbound i-motif. In vitro, iM-GNP resulted in a significant increase in r1 over a decreasing pH range (7.5–4.5) with a calculated pKa = 5.88 ± 0.01 and a 16.7% change per 0.1 pH unit. In comparison, a control CA with a non-responsive DNA strand (T33-GNP) did not show a significant change in r1 over the same pH range. The iM-GNP was further evaluated in 20% human serum and demonstrated a 28.14 ± 11.2% increase in signal from neutral pH to acidic pH. This approach paves a path for novel programmable, dynamic DNA-based complexes for τR-modulated bioresponsive MRI CAs.

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