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