Giordano Silvia, Pifferi Valentina, Morosi Lavinia, Morelli Melinda, Falciola Luigi, Cappelletti Giuseppe, Visentin Sonja, Licandro Simonetta A, Frapolli Roberta, Zucchetti Massimo, Pastorelli Roberta, Brunelli Laura, D'Incalci Maurizio, Davoli Enrico
Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
Nanomaterials (Basel). 2017 Mar 21;7(3):71. doi: 10.3390/nano7030071.
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice.
药物在组织内的成像对于肿瘤学至关重要,其目的是评估药物是否能以足够的浓度到达所有细胞以根除肿瘤。基质辅助激光解吸电离质谱成像(MALDI-MSI)是最有前景的成像技术之一,它能够同时可视化组织内的多种化合物。在开发MALDI-MSI方案的过程中,选择合适的基质是一个关键因素,因为基质的电离效率会根据分析物的结构及其物理化学性质而变化。本研究的目的是在药理学领域改进MALDI-MSI技术;开发专门设计的纳米结构表面,以实现对不同药物的高灵敏度和可重复性成像。在几种纳米材料中,我们测试了金纳米颗粒、钛纳米颗粒、埃洛石和碳纳米管作为可能的基质的性能。首先通过将所有纳米材料与药物共点样在MALDI板上进行筛选,评估药物信号强度和信噪比。对表现最佳的基质在对照肿瘤切片上进行测试,并与药物点样以检查生物基质的离子抑制作用。最后,将最佳的纳米材料用于对经治疗小鼠肿瘤内药物分布的初步研究。