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金纳米粒子与表皮生长因子和钆结合,用于磁共振成像中对比剂的精确递送。

Gold nanoparticles conjugated with epidermal growth factor and gadolinium for precision delivery of contrast agents in magnetic resonance imaging.

机构信息

Bionanotechnology Laboratory, Research and Development Institute, University of Vale do Paraíba, São José dos Campos, São Paulo, 12244000, Brazil.

Nanosensors Laboratory, Research and Development Institute, University of Vale do Paraiba, Sao Jose dos Campos, Sao Paulo, 12244000, Brazil.

出版信息

Radiol Phys Technol. 2024 Mar;17(1):153-164. doi: 10.1007/s12194-023-00761-y. Epub 2023 Nov 22.

Abstract

The utilization of contrast agents in magnetic resonance imaging (MRI) has become increasingly important in clinical diagnosis. However, the low diagnostic specificity of this technique is a limiting factor for the early detection of tumors. To develop a new contrast agent with a specific target for early stage tumors, we present the synthesis and characterization of a nanocontrast composed of gold nanoparticles (AuNPs), gadopentetic acid (Gd-DTPA), and epidermal growth factor (EGF). Carbodiimide-based chemistry was utilized to modify Gd-DTPA for functionalization with AuNPs. This resulted in the formation of the Au@Gd-EGF nanocontrast. The relaxation rate (1/T1) of the nanocontrast was analyzed using MRI, and cytotoxicity was determined based on cell viability and mitochondrial activity in a human breast adenocarcinoma cell line. Fourier-transform infrared spectroscopy analysis confirmed the effectiveness of carbodiimide in the formation of the Gd-DTPA-cysteamine complex in the presence of bands at 930, 1042, 1232, 1588, and 1716 cm. The complexes exhibited good interactions with the AuNPs. However, the signal intensity of the Au@Gd-EGF nanocontrast was lower than that of the commercial contrast agent because the r1/r2 relaxivities of the Gd-DTPA-based contrast agents were lower than those of the gadoversetamide-based molecules. The Au@Gd-EGF nanocontrast agent exhibited good biocompatibility, low cytotoxicity, and high signal intensity in MRI with active targeted delivery, suggesting significant potential for future applications in the early diagnosis of tumors.

摘要

在临床诊断中,磁共振成像(MRI)中对比剂的利用变得越来越重要。然而,该技术的低诊断特异性是早期检测肿瘤的一个限制因素。为了开发一种针对早期肿瘤的具有特定靶标的新型对比剂,我们提出了一种由金纳米颗粒(AuNPs)、钆喷替酸(Gd-DTPA)和表皮生长因子(EGF)组成的纳米对比剂的合成与表征。利用碳二亚胺化学对 Gd-DTPA 进行修饰,使其与 AuNPs 功能化。这导致了 Au@Gd-EGF 纳米对比剂的形成。利用 MRI 分析了纳米对比剂的弛豫率(1/T1),并根据人乳腺癌腺癌细胞系的细胞活力和线粒体活性测定了细胞毒性。傅里叶变换红外光谱分析证实了碳二亚胺在 Gd-DTPA-半胱氨酸复合物形成中的有效性,该复合物在 930、1042、1232、1588 和 1716 cm 处存在带。复合物与 AuNPs 表现出良好的相互作用。然而,由于基于 Gd-DTPA 的对比剂的 r1/r2 弛豫率低于基于加碘海醇的分子,因此 Au@Gd-EGF 纳米对比剂的信号强度低于商业对比剂。该 Au@Gd-EGF 纳米对比剂具有良好的生物相容性、低细胞毒性和 MRI 中的高信号强度,具有主动靶向递送功能,表明其在肿瘤早期诊断中的未来应用具有重要潜力。

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