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可经肾脏排泄的二硫化钼纳米颗粒作为双能乳腺X线摄影和计算机断层扫描的造影剂

Renally Excretable Molybdenum Disulfide Nanoparticles as Contrast Agents for Dual-Energy Mammography and Computed Tomography.

作者信息

Nieves Lenitza M, Berkow Emily K, Mossburg Katherine J, O Nathaniel H, Lau Kristen C, Rosario Derick N, Singh Priyash, Zhong Xingjian, Maidment Andrew D A, Cormode David P

机构信息

Department of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

出版信息

Bioconjug Chem. 2024 Dec 18;35(12):2006-2014. doi: 10.1021/acs.bioconjchem.4c00508. Epub 2024 Dec 4.

Abstract

Compared with conventional mammography, contrast-enhanced dual-energy mammography (DEM) can improve tumor detection for people with dense breasts. However, currently available iodine-based contrast agents have several drawbacks such as their contraindication for use with renal insufficiency, high-dose requirement, and suboptimal contrast production. Molybdenum disulfide nanoparticles (MoS NPs) have been shown to attenuate X-rays due to molybdenum's relatively high atomic number while having good biocompatibility. However, work exploring their use as X-ray contrast agents has been limited. In this study, we have developed a novel aqueous synthesis yielding ultrasmall, 2 nm MoS NPs with various small molecule coatings, including glutathione (GSH), penicillamine, and 2-mercaptopropionic acid (2MPA). These nanoparticles were shown to have low in vitro cytotoxicity when tested with various cell lines at concentrations up to 1 mg/mL. For the first time, these particles were shown to generate clinically relevant contrast in DEM. In DEM, MoS NPs generated higher contrast than iopamidol, a commercially available X-ray contrast agent, while also generating substantial contrast in CT. Moreover, MoS NPs demonstrated rapid elimination in vivo, mitigating long-term toxicity concerns. Together, the results presented here suggest the potential utility of MoS NPs as a dual-modality X-ray contrast agent for DEM and CT.

摘要

与传统乳腺钼靶检查相比,对比增强双能乳腺钼靶检查(DEM)可提高乳房致密人群的肿瘤检测率。然而,目前可用的碘基造影剂存在一些缺点,如肾功能不全患者禁用、需要高剂量以及造影效果欠佳。二硫化钼纳米颗粒(MoS NPs)因其钼的原子序数相对较高而能衰减X射线,同时具有良好的生物相容性。然而,探索其作为X射线造影剂用途的研究有限。在本研究中,我们开发了一种新型水相合成方法,可制备出具有各种小分子涂层(包括谷胱甘肽(GSH)、青霉胺和2-巯基丙酸(2MPA))的超小(2纳米)MoS NPs。当用浓度高达1毫克/毫升的各种细胞系进行测试时,这些纳米颗粒显示出低体外细胞毒性。首次证明这些颗粒在DEM中能产生临床相关的对比度。在DEM中,MoS NPs产生的对比度高于市售X射线造影剂碘帕醇,同时在CT中也能产生显著的对比度。此外,MoS NPs在体内显示出快速清除,减轻了对长期毒性的担忧。总之,本文呈现的结果表明MoS NPs作为用于DEM和CT的双模态X射线造影剂具有潜在用途。

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