A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging.
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.
Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. silvia.giordano@marionegri.it.
Silvia
S
Giordano
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. valentina.pifferi@unimi.it.
Valentina
V
Pifferi
Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. lavinia.morosi@marionegri.it.
Lavinia
L
Morosi
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. melinda.morelli@unimi.it.
Melinda
M
Morelli
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. luigi.falciola@unimi.it.
Luigi
L
Falciola
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. giuseppe.cappelletti@unimi.it.
Giuseppe
G
Cappelletti
Department of Molecular Biotechnology and Health Science, University of Torino, Via Nizza 52, 10126 Torino, Italy. sonja.visentin@unito.it.
Sonja
S
Visentin
Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. simonettaandrea.licandro@marionegri.it.
Simonetta A
SA
Licandro
Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. roberta.frapolli@marionegri.it.
Roberta
R
Frapolli
Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. massimo.zucchetti@marionegri.it.
Massimo
M
Zucchetti
Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. roberta.pastorelli@marionegri.it.
Roberta
R
Pastorelli
Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. laura.brunelli@marionegri.it.
Laura
L
Brunelli
Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. maurizio.dincalci@marionegri.it.
Maurizio
M
D'Incalci
Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. enrico.davoli@marionegri.it.
Enrico
E
Davoli
MALDI; TiO2; cancer imaging; gold nanoparticles; halloysite; mass spectrometry imaging