Abstract
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.
Highlights
In drug discovery and development it is important to understand the pharmacokinetics, investigating the absorption, distribution, metabolism, and excretion (ADME) of molecules.Several analytical methods, based on high-performance liquid chromatography (HPLC) and LiquidNanomaterials 2017, 7, 71; doi:10.3390/nano7030071 www.mdpi.com/journal/nanomaterialsNanomaterials 2017, 7, 71 chromatography tandem-mass spectrometry (LC-MS/MS), have been developed and employed on plasma and tissue homogenates to establish drug concentration profiles of drugs [1]
This is true in oncology where the data obtained may reveal very little about the drug’s ability to penetrate the tumor, because they neglect the information about the structure of the tumor microenvironment resulting in a loss of information about spatial distribution [2,3]
The main objective of this study is the improvement of the Matrix Assisted Laser Desorption Ionization (MALDI)-Mass spectrometry imaging (MSI) technique in the field of pharmacology, developing designed surfaces for the imaging of different anticancer drugs, with high spatial resolution, sensitivity, and reproducibility
Summary
In drug discovery and development it is important to understand the pharmacokinetics, investigating the absorption, distribution, metabolism, and excretion (ADME) of molecules.Several analytical methods, based on high-performance liquid chromatography (HPLC) and LiquidNanomaterials 2017, 7, 71; doi:10.3390/nano7030071 www.mdpi.com/journal/nanomaterialsNanomaterials 2017, 7, 71 chromatography tandem-mass spectrometry (LC-MS/MS), have been developed and employed on plasma and tissue homogenates to establish drug concentration profiles of drugs [1]. The manner in which a compound and its metabolites localize and distribute inside a tissue is important in order to ascertain whether they reach the intended target site. This is true in oncology where the data obtained may reveal very little about the drug’s ability to penetrate the tumor, because they neglect the information about the structure of the tumor microenvironment resulting in a loss of information about spatial distribution [2,3]. The imaging of drugs inside biological tissues is pivotal in oncology to assess whether a drug reaches high enough concentrations in all tumor cells and to develop new strategies to improve penetration and the outcome of chemotherapy [4]
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