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亲水量子点与 Gd(III)-DO3A 单酰胺螯合物功能化作为亮场和有效 T1/T2 双模态纳米探针。

Hydrophilic Quantum Dots Functionalized with Gd(III)-DO3A Monoamide Chelates as Bright and Effective T-weighted Bimodal Nanoprobes.

机构信息

Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, PE, Brazil.

Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE, Brazil.

出版信息

Sci Rep. 2019 Feb 20;9(1):2341. doi: 10.1038/s41598-019-38772-8.

DOI:10.1038/s41598-019-38772-8
PMID:30787475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6382838/
Abstract

Magnetic resonance imaging (MRI) is a powerful non-invasive diagnostic tool that enables distinguishing healthy from pathological tissues, with high anatomical detail. Nevertheless, MRI is quite limited in the investigation of molecular/cellular biochemical events, which can be reached by fluorescence-based techniques. Thus, we developed bimodal nanosystems consisting in hydrophilic quantum dots (QDs) directly conjugated to Gd(III)-DO3A monoamide chelates, a Gd(III)-DOTA derivative, allowing for the combination of the advantages of both MRI and fluorescence-based tools. These nanoparticulate systems can also improve MRI contrast, by increasing the local concentration of paramagnetic chelates. Transmetallation assays, optical characterization, and relaxometric analyses, showed that the developed bimodal nanoprobes have great chemical stability, bright fluorescence, and high relaxivities. Moreover, fluorescence correlation spectroscopy (FCS) analysis allowed us to distinguish nanosystems containing different amounts of chelates/QD. Also, inductively coupled plasma optical emission spectrometry (ICP - OES) indicated a conjugation yield higher than 75%. Our nanosystems showed effective longitudinal relaxivities per QD and per paramagnetic ion, at least 5 times [per Gd(III)] and 100 times (per QD) higher than the r for Gd(III)-DOTA chelates, suitable for T-weighted imaging. Additionally, the bimodal nanoparticles presented negligible cytotoxicity, and efficiently labeled HeLa cells as shown by fluorescence. Thus, the developed nanosystems show potential as strategic probes for fluorescence analyses and MRI, being useful for investigating a variety of biological processes.

摘要

磁共振成像(MRI)是一种强大的非侵入性诊断工具,能够以高解剖细节区分健康组织和病变组织。然而,MRI 在研究分子/细胞生化事件方面非常有限,这些事件可以通过荧光技术来实现。因此,我们开发了由亲水性量子点(QDs)直接与 Gd(III)-DO3A 单酰胺螯合物(一种 Gd(III)-DOTA 衍生物)偶联而成的双模态纳米系统,允许将 MRI 和荧光工具的优势结合起来。这些纳米颗粒系统还可以通过增加顺磁螯合物的局部浓度来提高 MRI 对比度。转金属化测定、光学特性和弛豫率分析表明,所开发的双模态纳米探针具有良好的化学稳定性、明亮的荧光和高弛豫率。此外,荧光相关光谱(FCS)分析允许我们区分含有不同数量螯合物/QD 的纳米系统。此外,电感耦合等离子体发射光谱(ICP-OES)表明偶联产率高于 75%。我们的纳米系统显示出每个 QD 和每个顺磁离子的有效纵向弛豫率,至少比 Gd(III)-DOTA 螯合物高 5 倍[每 Gd(III)]和 100 倍(每个 QD),适用于 T1 加权成像。此外,双模态纳米颗粒表现出可忽略不计的细胞毒性,并如荧光所示有效地标记了 HeLa 细胞。因此,所开发的纳米系统显示出作为荧光分析和 MRI 的潜在战略探针的潜力,对于研究各种生物过程非常有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/f72f28bcc586/41598_2019_38772_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/5af7fe60093a/41598_2019_38772_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/8fa9ce37ef4c/41598_2019_38772_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/ee22d603f809/41598_2019_38772_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/0273d7a628b7/41598_2019_38772_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/b01a701dd8e5/41598_2019_38772_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/f72f28bcc586/41598_2019_38772_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/5af7fe60093a/41598_2019_38772_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/8fa9ce37ef4c/41598_2019_38772_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/ee22d603f809/41598_2019_38772_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/0273d7a628b7/41598_2019_38772_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/b01a701dd8e5/41598_2019_38772_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/6382838/f72f28bcc586/41598_2019_38772_Fig6_HTML.jpg

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