Development of Laser Ionization Techniques for Evaluation of the Effect of Cancer Drugs Using Imaging Mass Spectrometry

Abstract

Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We investigated the use of imaging mass spectrometry (IMS) to simultaneously observe the distributions of an anticancer drug and photosensitizer administered to cancer cells. In particular, we sought to increase the sensitivity of detection of the anticancer drug docetaxel and the photosensitizer protoporphyrin IX (PpIX) by optimizing the ionization-assisting reagents. When we used a matrix consisting of equal weights of a zeolite (NaY5.6) and a conventional organic matrix (6-aza-2-thiothymine) in matrix-assisted laser desorption/ionization, the signal intensity of the sodium-adducted ion of docetaxel (administered at 100 μM) increased about 13-fold. Moreover, we detected docetaxel with the zeolite matrix using the droplet method, and detected PpIX by fluorescence and IMS with α-cyano-4-hydroxycinnamic acid (CHCA) using the spray method.

Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

“…There are numerous studies that explored the use of zeolites in medicine for imaging mass spectrometry, wound treatment, and drug delivery [ 32 , 33 , 34 , 35 , 36 ]. Zeolites are used as drug delivery systems for small molecules due to their unique porous characteristics and when the pore size can be matched to the size of drug molecules [ 35 ].…”

Enhancement of Ionization Efficiency Using Zeolite in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Multiple Drugs in Cancer Cells (Mass Spectrometry of Multiple Drugs in Cells Using Zeolite)

“…We previously reported that the signal intensity from a pure docetaxel sample at a concentration of 100 μM increased about 13-fold using a zeolite matrix with the droplet method. 13) In this study, we investigated two types of matrix application methods, the spray method and the droplet method. The matrix was sprayed using an airbrush (PS-153: 3500 PRO SPRAY Mk-2, Mr. Hobby, GSI Creos, Tokyo, Japan).…”

Development of Laser Ionization Imaging Mass Spectrometry for Multiple Drugs Administered to Cancer Cells

“…. Graduate School of Engineering, Osaka University, Suita, Osaka, Japan 2. Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan 3. Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo, Japan 4.…”

“…However, the detection sensitivity of IMS for drugs is lower than other drug imaging methods such as autoradiography, and some drugs could not effectively be ionized with MALDI. Therefore, a new ionization reagent, zeolite matrix, which is the mixture of zeolite and conventional MALDI matrix, has been developed to enhance the ionization efficiency of MALDI [1][2][3]. The detection sensitivity for an anticancer drug, docetaxel, was increased by 13-fold with the zeolite matrix [3].…”

“…Therefore, a new ionization reagent, zeolite matrix, which is the mixture of zeolite and conventional MALDI matrix, has been developed to enhance the ionization efficiency of MALDI [1][2][3]. The detection sensitivity for an anticancer drug, docetaxel, was increased by 13-fold with the zeolite matrix [3]. In this research, simultaneous imaging of an anticancer drug and a photosensitizing drug administered to cancer cells was investigated using the zeolite matrix to confirm that the photosensitizing drug could accumulate in anticancer drug resistant cancer cells.…”