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叶酸偶联 G-3 Tc-树枝状分子作为乳腺癌分子成像剂的合成、放射性标记及生物学评价。

Synthesis, radiolabelling, and biological assessment of folic acid-conjugated G-3 Tc-dendrimer as the breast cancer molecular imaging agent.

机构信息

Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Echocardiography Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

IET Nanobiotechnol. 2020 Sep;14(7):628-634. doi: 10.1049/iet-nbt.2020.0176.

DOI:10.1049/iet-nbt.2020.0176
PMID:33010140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8676428/
Abstract

Hence, in this study, the authors aimed to develop a dendrimer-based imaging agent comprised of poly(ethylene glycol) (PEG)-citrate, technetium-99 m (Tc), and folic acid. The dendrimer-G3 was synthesised and conjugated with folic acid, which confirmed by Fourier transform infrared, proton nuclear magnetic resonance, dynamic light scattering, and transition electron microscopy. 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-Tetrazolium-5-Carboxanilide cytotoxicity assay kit was used to measure the cellular toxicity of dendrimer. Imaging and biodistribution studies were conducted on the mice bearing tumour. The results showed that the fabricated dendrimer-G3 has a size of 90 ± 3 nm, which was increased to 100 ± 4 nm following the conjugation with folic acid. The radiostablity investigation showed that the fabricated dendrimers were stable in the human serum at various times. Toxicity assessment confirmed no cellular toxicity against HEK-293 cells at 0.25, 0.5, 1, 2, 4, and 8 mg/μl concentrations. The in vivo studies demonstrated that the synthesised dendrimers were able to provide a bright SPECT image applicable for tumour detection. In conclusion, the authors' study documented the positive aspects of PEG-citrate dendrimer conjugated with folic acid as the SPECT contrast agent for breast cancer detection.

摘要

因此,在这项研究中,作者旨在开发一种基于树枝状大分子的成像剂,由聚乙二醇(PEG)-柠檬酸、锝-99m(Tc)和叶酸组成。树枝状大分子 G3 被合成并与叶酸缀合,这一点通过傅里叶变换红外光谱、质子核磁共振、动态光散射和透射电子显微镜得到了证实。2,3-双-(2-甲氧基-4-硝基-5-磺苯基)-2H-四唑-5-羧基苯胺细胞毒性测定试剂盒用于测量树枝状大分子的细胞毒性。对荷瘤小鼠进行了成像和生物分布研究。结果表明,所制备的树枝状大分子 G3 的粒径为 90±3nm,与叶酸缀合后粒径增加到 100±4nm。放射稳定性研究表明,所制备的树枝状大分子在人血清中各时间点均稳定。毒性评估证实,在 0.25、0.5、1、2、4 和 8mg/μl 浓度下,对 HEK-293 细胞无细胞毒性。体内研究表明,所合成的树枝状大分子能够提供适用于肿瘤检测的明亮 SPECT 图像。总之,作者的研究记录了聚乙二醇-柠檬酸树枝状大分子与叶酸缀合作为乳腺癌检测 SPECT 对比剂的积极方面。