Kannen Hiroki, Miyoshi Yuto, Hazama Hisanao, Awazu Kunio
Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Global Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Mass Spectrom (Tokyo). 2021;10(1):A0099. doi: 10.5702/massspectrometry.A0099. Epub 2021 Dec 23.
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, FeO, and four types of TiO. 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 TiO at a 0.5 mg/mL concentration in 50% acetonitrile was increased by 1.6-fold compared to that without TiO. Changing the solvent to 90% acetonitrile gave a uniform TiO distribution and a 9-fold increase in the signal intensity for PpIX. Among the four types of TiO with different particle sizes and crystal structures, TiO 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 TiO provides effective ionization of the drug. In the future, we plan to investigate a spray method for the ionization of PpIX using TiO for the MSI of various drugs.
无标记质谱成像（MSI）在药物开发中具有更快筛选的潜力。通常使用基质辅助激光解吸/电离（MALDI），但其基质尺寸大且药物分布不均匀。使用纳米颗粒（NPs）的表面辅助激光解吸/电离（SALDI）可能会克服这些问题。在此，报道了NPs、溶剂比例和NPs滴加顺序对癌症药物原卟啉IX（PpIX）的SALDI-MSI的影响。使用浓度为10μM的PpIX在50%乙腈的50%水溶液中的溶液。NPs包括ZnO、FeO和四种类型的TiO。通过将它们溶解在90%乙腈水溶液中来制备NPs。使用波长为355nm的Nd:YAG激光的飞行时间质谱仪获得质谱。与不使用TiO相比，在50%乙腈中使用浓度为0.5mg/mL的TiO时信号强度提高了1.6倍。将溶剂改为90%乙腈可使TiO分布均匀，PpIX的信号强度提高9倍。在四种具有不同粒径和晶体结构的TiO中，粒径较小且具有金红石晶体结构的TiO产生的信号强度最高。在PpIX顶部形成一层也会导致信号强度增加。因此，使用TiO的SALDI可实现药物的有效电离。未来，我们计划研究一种使用TiO对PpIX进行电离的喷雾方法，用于各种药物的MSI。
