High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni

Mokosch, Annika; Gerbig, Stefanie; Grevelding, Christoph G.; Haeberlein, Simone; Spengler, Bernhard

doi:10.1007/s00216-021-03230-w

Cited by 19 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Scanning microprobe matrixassisted laser desorption ionization (SMALDI) mass was invented by Hubert, M. in 2002 (Spengler andHubert, 2002). It was further improved as atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry (AP-SMALDI MS) for imaging (Vegvari et al, 2017;Bhandari et al, 2018;Bredehoeft et al, 2019;Kadesch et al, 2020;Mokosch et al, 2021;Mueller et al, 2021;Righetti et al, 2021), while atmospheric pressure MALDI ion sources AP-MALDI have also been developed for MSI (Guenther et al, 2011;Jackson et al, 2018;Keller et al, 2018) and achieved a lateral resolution at 1.4 μm (Kompauer et al, 2017).…”

Section: Classical Ion Sourcesmentioning

confidence: 99%

“…Furthermore, MALDI ion resources can be easily coupled with high-resolution (resolving power) mass analyzers, such as TOF, FT-ICR, and Orbitrap, which provide high mass accuracy for MSI targets. During the recent years, with the developments of some new MALDI ion sources, such as atmosphere pressure AP-MALDI (Kompauer et al, 2017), AP-SMALDI (Vegvari et al, 2017;Bhandari et al, 2018;Bredehoeft et al, 2019;Kadesch et al, 2020;Mokosch et al, 2021;Mueller et al, 2021;Righetti et al, 2021), MALDI-2 (Soltwisch et al, 2015), transmission MALDI-2 (Niehaus et al, 2019), and nano laser probed-based laser desorption ionization (Meng et al, 2020), the lateral resolution of MALDI-MSI will possibly achieve nm or µm level for single cell and even subcellular scale imaging. Finally, the scanning speed of MALDI-MSI largely depends on the speed of MS detection, spectra recording and data processing.…”

Section: General Marks and Conclusionmentioning

confidence: 99%

See 1 more Smart Citation

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Zhu

Chen

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still the most widespread MSI scanning method. Here, we aim to provide a comprehensive review of MALDI-MSI with an emphasis on its advances of the instrumentation, methods, application, and future directions in single cell and biological tissues.

show abstract

Section: Classical Ion Sourcesmentioning

confidence: 99%

Section: General Marks and Conclusionmentioning

confidence: 99%

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Zhu

Chen

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…Due to the larger body size of F. hepatica, discrimination of organs by markers is significantly easier than in S. mansoni, a related trematode species for which we previously established AP-SMALDI MSI of the kinase inhibitor imatinib and identified lipid markers for its ovary and tegument (Kadesch et al 2020;Mokosch et al 2021). Therefore, AP-SMALDI-based drug-imaging experiments that aim at investigating drug tissue tropism, and lipid profiles of specific tissues are even more informative for F. hepatica.…”

Section: Organ Assignment Within the Section Using Lipid Marker Signa...mentioning

confidence: 99%

“…In addition, the spatial resolution of PET is limited to the low millimeter-range making drug distribution studies on such small samples impossible (Watakabe et al 2020). Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a cuttingedge method in the fields of life sciences and biomedicine that we recently adopted and optimized for the purpose of drug imaging in trematode parasites (Mokosch et al 2021;Morawietz et al 2020). MALDI MSI is a powerful technique that integrates molecular imaging and advanced image analysis.…”

Section: Introductionmentioning

confidence: 99%

Spatial visualization of drug uptake and distribution in Fasciola hepatica using high-resolution AP-SMALDI mass spectrometry imaging

et al. 2022

Self Cite

View full text Add to dashboard Cite

Understanding drug penetration, distribution, and metabolization is fundamental for understanding drug efficacy. This also accounts for parasites during antiparasitic treatment. Recently, we established matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in blood flukes and liver flukes. This label-free technique is capable of visualizing the molecular distribution of endogenous and exogenous molecules, such as drug compounds. Here, we conducted atmospheric-pressure scanning microprobe MALDI MSI (AP-SMALDI MSI) of tissue sections of adult Fasciola hepatica that have been treated in vitro with 100 µM of triclabendazole (TCBZ), the drug of choice for treatment of fasciolosis, and its main metabolite triclabendazole sulfoxide (TCBZ-SO). Measurements covered an m/z mass range of 250–1,000 and provided a high spatial resolution using a pixel size of 10 µm. To support the interpretation of drug distribution, we first identified endogenous lipids that mark characteristic tissues such as the gastrodermis, the tegument, and the parenchyma. The obtained results suggested an early tegumental route of TCBZ uptake within 20 min, followed by spreading throughout the parasite after 4 h, and an even distribution in most tissues after 12 h. This coincided with a strong reduction of parasite vitality. TCBZ-SO treatment demonstrated the accumulation of this metabolite in the same tissues as the parent drug compound. These data demonstrate the auspicious potential of MALDI MSI to visualize uptake and distribution patterns of drugs or drug-candidate compounds in parasites, which might contribute to preclinical drug discovery in liver fluke research and beyond.

show abstract

“…If trans-bilayer permeability were significant in real biomembranes, the free concentrations of drugs inside cells and organelles (modulo pH and potential gradients) would be more or less homogeneous. Of course, they are not, as is well-known (and as can easily be determined by chemical imaging methods, e.g., [ 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 ]). A particularly well-established case is that of the blood–brain barrier, where, despite the lipids not being noticeably different from those in other cells, the permeability is negligible if specific transporters are not involved [ 160 , 161 , 162 , 163 , 164 ].…”

Section: Introductionmentioning

confidence: 99%

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Kell

2021

Molecules

View full text Add to dashboard Cite

Over the years, my colleagues and I have come to realise that the likelihood of pharmaceutical drugs being able to diffuse through whatever unhindered phospholipid bilayer may exist in intact biological membranes in vivo is vanishingly low. This is because (i) most real biomembranes are mostly protein, not lipid, (ii) unlike purely lipid bilayers that can form transient aqueous channels, the high concentrations of proteins serve to stop such activity, (iii) natural evolution long ago selected against transport methods that just let any undesirable products enter a cell, (iv) transporters have now been identified for all kinds of molecules (even water) that were once thought not to require them, (v) many experiments show a massive variation in the uptake of drugs between different cells, tissues, and organisms, that cannot be explained if lipid bilayer transport is significant or if efflux were the only differentiator, and (vi) many experiments that manipulate the expression level of individual transporters as an independent variable demonstrate their role in drug and nutrient uptake (including in cytotoxicity or adverse drug reactions). This makes such transporters valuable both as a means of targeting drugs (not least anti-infectives) to selected cells or tissues and also as drug targets. The same considerations apply to the exploitation of substrate uptake and product efflux transporters in biotechnology. We are also beginning to recognise that transporters are more promiscuous, and antiporter activity is much more widespread, than had been realised, and that such processes are adaptive (i.e., were selected by natural evolution). The purpose of the present review is to summarise the above, and to rehearse and update readers on recent developments. These developments lead us to retain and indeed to strengthen our contention that for transmembrane pharmaceutical drug transport “phospholipid bilayer transport is negligible”.

show abstract

High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni

Cited by 19 publications

References 47 publications

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Spatial visualization of drug uptake and distribution in Fasciola hepatica using high-resolution AP-SMALDI mass spectrometry imaging

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes

Contact Info

Product

Resources

About