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在癌细胞中多种药物的基质辅助激光解吸/电离质谱分析中使用沸石提高电离效率(使用沸石对细胞中多种药物进行质谱分析)

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).

作者信息

Kannen Hiroki, Nomura Shusei, Hazama Hisanao, Kaneda Yasufumi, Fujino Tatsuya, Awazu Kunio

机构信息

Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.

Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Mass Spectrom (Tokyo). 2020;9(1):A0091. doi: 10.5702/massspectrometry.A0091. Epub 2020 Dec 4.

DOI:10.5702/massspectrometry.A0091
PMID:33299734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7708746/
Abstract

Combined therapy using photodynamic therapy (PDT) and chemotherapy has been proposed for anticancer-drug-resistant cancer cells. To evaluate the efficacy of such a combined therapy, the uptakes of an anticancer drug and a photosensitizer in cancer cells must be assessed. Mass spectrometry using matrix-assisted laser desorption/ionization can detect multiple drugs simultaneously. Human prostate cancer cells PC-3 or docetaxel-resistant cancer cells PC-3-DR were incubated in a serum-free medium containing a photosensitizer, protoporphyrin IX (PpIX), and an anticancer drug, docetaxel. A zeolite matrix was created by mixing 6-aza-2-thiothymine and NaY5.6 zeolite, and dissolving in water with 50% acetone. Ions were obtained with a time-of-flight mass spectrometer using a Nd:YAG laser at a wavelength of 355 nm. The cell morphology was preserved by washing the cells with ammonium acetate and drying in a vacuum after drug administration. Protonated PpIX (/ 563.3) and the sodium adduct ion of docetaxel (/ 829.9) were obtained from PC-3 cells simultaneously using the zeolite matrix. On the other hand, PpIX was detected but ions originating from docetaxel were not detected from PC-3-DR cells. The result indicated the efficacy of PDT for docetaxel-resistant cancer cells.

摘要

已提出使用光动力疗法(PDT)和化疗的联合疗法来治疗对抗癌药耐药的癌细胞。为了评估这种联合疗法的疗效,必须评估癌细胞中抗癌药物和光敏剂的摄取情况。使用基质辅助激光解吸/电离的质谱分析可以同时检测多种药物。将人前列腺癌细胞PC-3或多西他赛耐药癌细胞PC-3-DR在含有光敏剂原卟啉IX(PpIX)和抗癌药物多西他赛的无血清培养基中孵育。通过将6-氮杂-2-硫代胸腺嘧啶与NaY5.6沸石混合,并溶解在含50%丙酮的水中来制备沸石基质。使用波长为355 nm的Nd:YAG激光,通过飞行时间质谱仪获得离子。给药后,用醋酸铵洗涤细胞并真空干燥,从而保存细胞形态。使用沸石基质同时从PC-3细胞中获得质子化的PpIX(/ 563.3)和多西他赛的钠加合离子(/ 829.9)。另一方面,从PC-3-DR细胞中检测到了PpIX,但未检测到源自多西他赛的离子。该结果表明了光动力疗法对多西他赛耐药癌细胞的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/70dadcc70573/massspectrometry-9-1-A0091-figure07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/767815e3c0ad/massspectrometry-9-1-A0091-figure01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/96dd2b75ce23/massspectrometry-9-1-A0091-figure02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/8d71f91287b4/massspectrometry-9-1-A0091-figure03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/b542b1e85e42/massspectrometry-9-1-A0091-figure04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/d3cf33bc8fd9/massspectrometry-9-1-A0091-figure05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/6340c3229dd5/massspectrometry-9-1-A0091-figure06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/70dadcc70573/massspectrometry-9-1-A0091-figure07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/767815e3c0ad/massspectrometry-9-1-A0091-figure01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/96dd2b75ce23/massspectrometry-9-1-A0091-figure02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/8d71f91287b4/massspectrometry-9-1-A0091-figure03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/b542b1e85e42/massspectrometry-9-1-A0091-figure04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/d3cf33bc8fd9/massspectrometry-9-1-A0091-figure05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/6340c3229dd5/massspectrometry-9-1-A0091-figure06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a4/7708746/70dadcc70573/massspectrometry-9-1-A0091-figure07.jpg

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