Improvement in Ionization Efficiency Using Metal Oxide Nanoparticles in Laser Desorption/Ionization Mass Spectrometry of a Cancer Drug.

Mass spectrometry imaging (MSI) without labeling has the potential for faster screening in drug development. Matrix-assisted laser desorption/ionization (MALDI) is typically used, but it has a large matrix size and uneven drug distribution. Surface-assisted laser desorption/ionization (SALDI) using nanoparticles (NPs) may overcome these issues. Here, the influence of NPs, solvent ratio, and order of dropping of NPs on SALDI-MSI of protoporphyrin IX (PpIX), a cancer drug, are reported. A solution of PpIX in a 50% aqueous solution of 50% acetonitrile at a concentration of 10 μM was used. The NPs include ZnO, Fe₃O₄, and four types of TiO₂. The NPs were fabricated by dissolving them on an aqueous 90% acetonitrile solution. Mass spectra were obtained with a time-of-flight mass spectrometer using a Nd:YAG laser at a 355-nm wavelength. The signal intensity using TiO₂ at a 0.5 mg/mL concentration in 50% acetonitrile was increased by 1.6-fold compared to that without TiO₂. Changing the solvent to 90% acetonitrile gave a uniform TiO₂ distribution and a 9-fold increase in the signal intensity for PpIX. Among the four types of TiO₂ with different particle sizes and crystal structures, TiO₂ with a smaller particle size and a rutile crystal structure produced the highest signal intensity. Forming a layer on top of the PpIX also resulted in an increased signal intensity. Hence, SALDI using TiO₂ provides effective ionization of the drug. In the future, we plan to investigate a spray method for the ionization of PpIX using TiO₂ for the MSI of various drugs.