Department of Biomedical Engineering, Groningen University, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AW Groningen, Netherlands.
Institute of Metallurgy and Materials Science Polish Academy of Sciences, 25 Reymonta Street, 30-059, Cracow, Poland.
ACS Appl Mater Interfaces. 2022 Aug 31;14(34):39265-39273. doi: 10.1021/acsami.2c11688. Epub 2022 Aug 19.
Here, we present multifunctional fluorescent nanodiamonds (FNDs) for simultaneous drug delivery and free radical detection. For this purpose, we modified FNDs containing nitrogen vacancy (NV) centers with a diazoxide derivative. We found that our particles enter cells more easily and are able to deliver this cancer drug into HeLa cells. The particles were characterized by infrared spectroscopy, dynamic light scattering, and secondary electron microscopy. Compared to the free drug, we observe a sustained release over 72 h rather than 12 h for the free drug. Apart from releasing the drug, with these particles, we can measure the drug's effect on free radical generation directly. This has the advantage that the response is measured locally, where the drug is released. These FNDs change their optical properties based on their magnetic surrounding. More specifically, we make use of a technique called relaxometry to detect spin noise from the free radical at the nanoscale with subcellular resolution. We further compared the results from our new technique with a conventional fluorescence assay for the detection of reactive oxygen species. This provides a new method to investigate the relationship between drug release and the response by the cell via radical formation or inhibition.
在这里,我们展示了多功能荧光纳米金刚石(FNDs),可用于同时进行药物输送和自由基检测。为此,我们用一种二氮嗪衍生物对含有氮空位(NV)中心的 FNDs 进行了修饰。我们发现,我们的粒子更容易进入细胞,并能够将这种癌症药物递送到 HeLa 细胞中。这些粒子通过红外光谱、动态光散射和二次电子显微镜进行了表征。与游离药物相比,我们观察到药物在 72 小时内持续释放,而游离药物仅在 12 小时内释放。除了释放药物之外,使用这些粒子,我们还可以直接测量药物对自由基生成的影响。这具有测量反应发生在药物释放的局部位置的优点。这些 FNDs 根据其磁环境改变其光学性质。更具体地说,我们利用一种称为弛豫测量的技术,以亚细胞分辨率检测来自纳米尺度上自由基的自旋噪声。我们进一步将我们新技术的结果与传统的荧光测定法用于检测活性氧物质进行了比较。这提供了一种新的方法来研究药物释放与通过自由基形成或抑制引起的细胞反应之间的关系。