Drugs distribution assessment in solid tumor tissues : an advanced Imaging Mass Spectrometry analysis

Drugs imaging is pivotal in oncology where the achievement of a homogeneous drug distribution within tumor tissue is crucial for therapy. The use of nanoparticles (NPs) as matrixes in MALDI-MS imaging has opened up new opportunities thanks to the almost complete absence of background signals from matrix degradation. Among nanoparticles, inorganic ones characterized by high photo-adsorption, low heat capacity and large surface area, can assure rapid heating, highly localized and uniform energy deposition, affording efficient sample desorption and ionization. Here, different inorganic nanomaterials (titania, gold, carbon nanotubes, halloysite) were studied and compared as matrices in the development of MALDI supports for the ionization of several anticancer drugs (Paclitaxel, Ortataxel, Trabectedin, Imatinib, Lucitanib and Doxorubicin) to study their tumor distribution in xenografts with high resolution and sensitivity. The efficiency of different nanostructured matrixes was evaluated spotting the same concentration of five anticancer drugs on MALDI plate, on control tumor tissues and by spraying them on treated tumors. The results show that TiO2 nanoparticles and Carbon nanotubes efficiently ionize and fragment Paclitaxel in the ion source. Particularly, P25 TiO2-NPs based matrix seems to be the best one to visualize Paclitaxel distribution with high sensitivity. Halloysite matrix gives the worst results, while gold nanoparticles allows to ionize almost all tested drugs both on MALDI plate and on control tissues.