Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects
Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects
复制标题
DOI：
10.1021/acs.analchem.9b04398
复制
发表时间：
2020-01-21
影响因子：
7.4
通讯作者：
Vachet, Richard W.
中科院分区：
文献类型：
--
作者：
Sikora, Kristen N.;Hardie, Joseph M.;Vachet, Richard W.
基于纳米材料的药物输送载体能够以受控的、有针对性的方式输送治疗药物。然而，目前能够同时检测纳米材料分布及其生化效应的分析方法有限。在这项研究中，我们证明了基质辅助激光解吸/电离质谱仪成像(MALDI-MSI)和激光烧蚀电感耦合等离子体质谱成像(LA-ICP-MSI)可以结合使用来获得纳米材料的分布和生化结果。这些研究使用了装载siRNA的纳米颗粒稳定胶囊(NPSCs)作为试验床。在静脉注射小鼠的脾组织上进行的MALDI-MSI实验表明，根据已知的受肿瘤坏死因子-α影响的途径，携带抗肿瘤坏死因子-αsiRNA的NPSCs会引起脾白髓区域脂质成分的变化，这是预期的，而携带杂乱siRNA的NPSCs不会引起预测的变化。有趣的是，LA-ICP-MSI实验显示NPSCs主要定位于红髓，这表明观察到的脂质成分的变化是由于对肿瘤坏死因子-α的产生的扩散而不是局部影响。这样的信息只能通过组合来自两个模式的数据来获取，我们通过使用来自MALDI-MSI的血红素信号和来自LA-ICP-MSI的铁信号来覆盖图像来实现这一点。在发现NPSCs的区域，脂质成分也发生了一些意想不到的变化，这表明NPSCs本身也可以影响组织生化。
Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-alpha siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-alpha, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-alpha production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.