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质谱成像技术前沿进展及其在药物研究中的应用

王颂凯, 邹宇琛, 孙士鹏, 闫郅烨, 汤维维, 李萍, 李彬

王颂凯, 邹宇琛, 孙士鹏, 闫郅烨, 汤维维, 李萍, 李彬. 质谱成像技术前沿进展及其在药物研究中的应用[J]. 中国药科大学学报, 2023, 54(6): 653-661. DOI: 10.11665/j.issn.1000-5048.2023091901
引用本文: 王颂凯, 邹宇琛, 孙士鹏, 闫郅烨, 汤维维, 李萍, 李彬. 质谱成像技术前沿进展及其在药物研究中的应用[J]. 中国药科大学学报, 2023, 54(6): 653-661. DOI: 10.11665/j.issn.1000-5048.2023091901
shu
WANG Songkai, ZOU Yuchen, SUN Shipeng, YAN Zhiye, TANG Weiwei, LI Ping, LI Bin. Recent advances in mass spectrometry imaging and its application in drug research[J]. Journal of China Pharmaceutical University, 2023, 54(6): 653-661. DOI: 10.11665/j.issn.1000-5048.2023091901
Citation: WANG Songkai, ZOU Yuchen, SUN Shipeng, YAN Zhiye, TANG Weiwei, LI Ping, LI Bin. Recent advances in mass spectrometry imaging and its application in drug research[J]. Journal of China Pharmaceutical University, 2023, 54(6): 653-661. DOI: 10.11665/j.issn.1000-5048.2023091901
shu

质谱成像技术前沿进展及其在药物研究中的应用

  • 1.

    中国药科大学多靶标天然药物全国重点实验室，南京 211198

  • 2.

    中国药科大学中药学院，南京 211198

基金项目: 国家自然科学基金资助项目（No.82374028）

Recent advances in mass spectrometry imaging and its application in drug research

  • 1.

    State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198

  • 2.

    School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.82374028)

摘要

    摘要
  • 摘要: 质谱成像（MSI）作为一种无标记的分子成像技术，弥补了传统液质联用等分析技术空间分辨能力的不足，已被广泛应用于小分子代谢物、脂质、多肽及蛋白质的组织分布研究。随着MSI技术灵敏度和空间分辨率的不断提高，该技术在精确定位药物组织分布、可视化药物代谢过程、追踪药物递送等研究领域备受关注，为药物临床前研究提供了新技术和新方法。本文介绍了多种常见MSI技术的基本原理、技术关键参数、技术优势与不足，重点综述了近年来MSI技术在药物有效性及安全性评价、药物组织分布研究、药物递送、中药分析等领域的应用，以期拓展MSI技术在药物研发中的应用，推动药物研发进程。
    Abstract: Mass spectrometry imaging (MSI), a label-free molecular imaging technique, has been applied widely in the spatial localization of small molecule metabolites, lipids, peptides, and proteins, with its unique advantage of high spatial resolving power compared to traditional liquid chromatography-mass spectrometry (LC-MS).With the nonstop advancement of its achievable sensitivity and spatial resolution, MSI technique has been providing novel perspectives into the preclinical studies of drugs, such as in vivo localization of drugs and their metabolites, visualization of drug metabolism, and drug delivery tracking.This review introduces the basics of MSI techniques, including basic principles, key features, technical advantages, and limitations, with particular highlight of the recent applications of MSI in drug efficacy and safety evaluation, drug distribution research, drug delivery research, and analysis of Chinese medicine from recent publications, aiming to promote the utilization and further expansion of MSI in the research and development of drugs.
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  • [1] Refaat A, Yap ML, Pietersz G, et al. In vivo fluorescence imaging: success in preclinical imaging paves the way for clinical applications[J]. J Nanobiotechnology, 2022, 20(1): 450.
    [2] Kenry, Duan YK, Liu B. Recent advances of optical imaging in the second near-infrared window[J]. Adv Mater, 2018, 30(47): e1802394.
    [3] Siddhanta S, Kuzmin AN, Pliss A, et al. Advances in Raman spectroscopy and imaging for biomedical research[J]. Adv Opt Photon, 2023, 15(2): 318-384.
    [4] Angel PM, Baldwin HS, Sen DG, et al. Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve[J]. Biochim Biophys Acta Proteins Proteom, 2017, 1865(7): 927-935.
    [5] Li KN, Guo S, Tang WW, et al. Characterizing the spatial distribution of dipeptides in rodent tissue using MALDI MS imaging with on-tissue derivatization[J]. Chem Commun, 2021, 57(93): 12460-12463.
    [6] Dufresne M, Fincher JA, Patterson NH, et al. α-cyano-4-hydroxycinnamic acid and tri-potassium citrate salt pre-coated silicon nanopost array provides enhanced lipid detection for high spatial resolution MALDI imaging mass spectrometry[J]. Anal Chem, 2021, 93(36): 12243-12249.
    [7] Wang XN, Li B. Monolithic gold nanoparticles/thiol-β-cyclodextrin- functionalized TiO2 nanowires for enhanced SALDI MS detection and imaging of natural products[J]. Anal Chem, 2022, 94(2): 952-959.
    [8] Bryant RN, Jones C, Raven MR, et al. Sulfur isotope analysis of microcrystalline iron sulfides using secondary ion mass spectrometry imaging: extracting local paleo-environmental information from modern and ancient sediments[J]. Rapid Commun Mass Spectrom, 2019, 33(5): 491-502.
    [9] Dunham SJB, Ellis JF, Baig NF, et al. Quantitative SIMS imaging of agar-based microbial communities[J]. Anal Chem, 2018, 90(9): 5654-5663.
    [10] Yan X, Zhao XA, Zhou ZP, et al. Cell-type-specific metabolic profiling achieved by combining desorption electrospray ionization mass spectrometry imaging and immunofluorescence staining[J]. Anal Chem, 2020, 92(19): 13281-13289.
    [11] Castellanos A, Ramirez CE, Michalkova V, et al. Three dimensional secondary ion mass spectrometry imaging (3D-SIMS) of Aedes aegypti ovarian follicles[J]. J Anal At Spectrom, 2019, 34(5): 874-883.
    [12] Passarelli MK, Pirkl A, Moellers R, et al. The 3D OrbiSIMS-label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power[J]. Nat Methods, 2017, 14(12): 1175-1183.
    [13] Bredeh?ft J, Bhandari DR, Pflieger FJ, et al. Visualizing and profiling lipids in the OVLT of fat-1 and wild type mouse brains during LPS-induced systemic inflammation using AP-SMALDI MSI[J]. ACS Chem Neurosci, 2019, 10(10): 4394-4406.
    [14] Li B, Sun RY, Gordon A, et al. 3-aminophthalhydrazide (luminol) As a matrix for dual-polarity MALDI MS imaging[J]. Anal Chem, 2019, 91(13): 8221-8228.
    [15] Tang WW, Gordon A, Wang F, et al. Hydralazine as a versatile and universal matrix for high-molecular coverage and dual-polarity matrix-assisted laser desorption/ionization mass spectrometry imaging[J]. Anal Chem, 2021, 93(26): 9083-9093.
    [16] Shariatgorji M, Nilsson A, Fridjonsdottir E, et al. Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging[J]. Nat Methods, 2019, 16(10): 1021-1028.
    [17] Ferreira MS, de Oliveira DN, Mesquita CC, et al. MALDI-MSI: a fast and reliable method for direct melatonin quantification in biological fluids[J]. J Anal Sci Technol, 2016, 7: 1-6.
    [18] Heijs B, Potthoff A, Soltwisch J, et al. MALDI-2 for the enhanced analysis of N-linked glycans by mass spectrometry imaging[J]. Anal Chem, 2020, 92(20): 13904-13911.
    [19] Chingin K, Gamez G, Chen HW, et al. Rapid classification of perfumes by extractive electrospray ionization mass spectrometry (EESI-MS)[J]. Rapid Commun Mass Spectrom, 2008, 22(13): 2009-2014.
    [20] Chen HW, Wortmann A, Zhang WH, et al. Rapid in vivo fingerprinting of nonvolatile compounds in breath by extractive electrospray ionization quadrupole time-of-flight mass spectrometry[J]. Angew Chem Int Ed Engl, 2007, 46(4): 580-583.
    [21] Harper JD, Charipar NA, Mulligan CC, et al. Low-temperature plasma probe for ambient desorption ionization[J]. Anal Chem, 2008, 80(23): 9097-9104.
    [22] Luo ZG, He JM, Chen Y, et al. Air flow-assisted ionization imaging mass spectrometry method for easy whole-body molecular imaging under ambient conditions[J]. Anal Chem, 2013, 85(5): 2977-2982.
    [23] Liu CY, Qi KK, Yao L, et al. Imaging of polar and nonpolar species using compact desorption electrospray ionization/postphotoionization mass spectrometry[J]. Anal Chem, 2019, 91(10): 6616-6623.
    [24] Sikora KN, Hardie JM, Castellanos-García LJ, et al. Dual mass spectrometric tissue imaging of nanocarrier distributions and their biochemical effects[J]. Anal Chem, 2020, 92(2): 2011-2018.
    [25] Chen YW, Hu DJ, Zhao LS, et al. Unraveling metabolic alterations in transgenic mouse model of Alzheimer’s disease using MALDI MS imaging with 4-aminocinnoline-3-carboxamide matrix[J]. Anal Chim Acta, 2022, 1192: 339337.
    [26] Nilsson A, Goodwin RJA, Shariatgorji M, et al. Mass spectrometry imaging in drug development[J]. Anal Chem, 2015, 87(3): 1437-1455.
    [27] Guo S, Li KN, Chen YW, et al. Unraveling the drug distribution in brain enabled by MALDI MS imaging with laser-assisted chemical transfer[J]. Acta Pharm Sin B, 2022, 12(4): 2120-2126.
    [28] Meng YF, Gao CH, Lu Q, et al. Single-cell mass spectrometry imaging of multiple drugs and nanomaterials at organelle level[J]. ACS Nano, 2021, 15(8): 13220-13229.
    [29] Yin ZB, Cheng XL, Liu R, et al. Chemical and topographical single-cell imaging by near-field desorption mass spectrometry[J]. Angew Chem Int Ed Engl, 2019, 58(14): 4541-4546.
    [30] Caprioli RM. Imaging mass spectrometry: molecular microscopy for the new age of biology and medicine[J]. Proteomics, 2016, 16(11/12): 1607-1612.
    [31] Haque MIU, Mukherjee D, Stopka SA, et al. Deep learning on multimodal chemical and whole slide imaging data for predicting prostate cancer directly from tissue images[J]. J Am Soc Mass Spectrom, 2023, 34(2): 227-235.
    [32] Unsihuay D, Yin RC, Sanchez DM, et al. High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry[J]. Anal Chim Acta, 2021, 1186: 339085.
    [33] Xie CY, Chen YY, Wang XX, et al. Chiral derivatization-enabled discrimination and on-tissue detection of proteinogenic amino acids by ion mobility mass spectrometry[J]. Chem Sci, 2022, 13(47): 14114-14123.
    [34] Ellis SR, Paine MRL, Eijkel GB, et al. Automated, parallel mass spectrometry imaging and structural identification of lipids[J]. Nat Methods, 2018, 15(7): 515-518.
    [35] Guo XY, Cao WB, Fan XM, et al. Tandem mass spectrometry imaging enables high definition for mapping lipids in tissues[J]. Angew Chem Int Ed Engl, 2023, 62(9): e202214804.
    [36] Han YH, Zhao YS, Chen PP, et al. On-tissue derivatization for isomer-specific mass spectrometry imaging and relative quantification of monosaccharides in biological tissues[J]. Anal Chim Acta, 2022, 1225: 340241.
    [37] Wu Q. A review on quantitation-related factors and quantitation strategies in mass spectrometry imaging of small biomolecules[J]. Anal Methods, 2022, 14(40): 3932-3943.
    [38] Unsihuay D, Mesa Sanchez D, Laskin J. Quantitative mass spectrometry imaging of biological systems[J]. Annu Rev Phys Chem, 2021, 72: 307-329.
    [39] Schulz S, Becker M, Groseclose MR, et al. Advanced MALDI mass spectrometry imaging in pharmaceutical research and drug development[J]. Curr Opin Biotechnol, 2019, 55: 51-59.
    [40] Takai N, Tanaka Y, Watanabe A, et al. Quantitative imaging of a therapeutic peptide in biological tissue sections by MALDI MS[J]. Bioanalysis, 2013, 5(5): 603-612.
    [41] Torok S, Rezeli M, Kelemen O, et al. Limited tumor tissue drug penetration contributes to primary resistance against angiogenesis inhibitors[J]. Theranostics, 2017, 7(2): 400-412.
    [42] Munteanu B, Meyer B, von Reitzenstein C, et al. Label-free in situ monitoring of histone deacetylase drug target engagement by matrix-assisted laser desorption ionization-mass spectrometry biotyping and imaging[J]. Anal Chem, 2014, 86(10): 4642-4647.
    [43] Mittal P, Price ZK, Lokman NA, et al. Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for monitoring of drug response in primary cancer spheroids[J]. Proteomics, 2019, 19, 1900146.
    [44] Jaeschke H, Knight TR, Bajt ML. The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity[J]. Toxicol Lett, 2003, 144(3): 279-288.
    [45] Sezgin S, Hassan R, Zühlke S, et al. Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI[J]. Arch Toxicol, 2018, 92(9): 2963-2977.
    [46] Li LM, Zang QC, Li XZ, et al. Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids[J]. J Pharm Anal, 2023, 13(5): 483-493.
    [47] Wang ZH, He BS, Liu YQ, et al. In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging[J]. Acta Pharm Sin B, 2020, 10(6): 1083-1093.
    [48] Nilsson A, Forngren B, Bjurstr?m S, et al. In situ mass spectrometry imaging and ex vivo characterization of renal crystalline deposits induced in multiple preclinical drug toxicology studies[J]. PLoS One, 2012, 7(10): e47353.
    [49] Barrette AM, Roberts JK, Chapin C, et al. Antiinflammatory effects of budesonide in human fetal lung[J]. Am J Respir Cell Mol Biol, 2016, 55(5): 623-632.
    [50] Zecchi R, Franceschi P, Tigli L, et al. Surfactant-assisted distal pulmonary distribution of budesonide revealed by mass spectrometry imaging[J]. Pharmaceutics, 2021, 13(6): 868.
    [51] Tannock IF, Lee CM, Tunggal JK, et al. Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy[J]. Clin Cancer Res, 2002, 8(3): 878-884.
    [52] Tanaka Y, Hirata M, Shinonome S, et al. Distribution analysis of epertinib in brain metastasis of HER2-positive breast cancer by imaging mass spectrometry and prospect for antitumor activity[J]. Sci Rep, 2018, 8(1): 343.
    [53] Tang WW, Zhang YJ, Li P, et al. Evaluation of intestinal drug absorption and interaction using quadruple single-pass intestinal perfusion coupled with mass spectrometry imaging[J]. Anal Chem, 2023, 95(6): 3218-3227.
    [54] Aikawa H, Hayashi M, Ryu S, et al. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging[J]. Sci Rep, 2016, 6: 23749.
    [55] Moraleja I, Esteban-Fernández D, Lázaro A, et al. Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin[J]. Anal Bioanal Chem, 2016, 408(9): 2309-2318.
    [56] Ding YX, Xu YJ, Yang WZ, et al. Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy[J]. Nano Today, 2020, 35: 100970.
    [57] Ryu S, Ohuchi M, Yagishita S, et al. Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging[J]. Sci Rep, 2020, 10(1): 15535.
    [58] Xue JJ, Liu HH, Chen SM, et al. Mass spectrometry imaging of the in situ drug release from nanocarriers[J]. Sci Adv, 2018, 4(10): eaat9039.
    [59] Strittmatter N, Moss JI, Race AM, et al. Multi-modal molecular imaging maps the correlation between tumor microenvironments and nanomedicine distribution[J]. Theranostics, 2022, 12(5): 2162-2174.
    [60] Meng YF, Cheng XL, Wang TT, et al. Micro-lensed fiber laser desorption mass spectrometry imaging reveals subcellular distribution of drugs within single cells[J]. Angew Chem Int Ed Engl, 2020, 59(41): 17864-17871.
    [61] Pena-Rodríguez E, García-Berrocoso T, Fernández EV, et al. Monitoring dexamethasone skin biodistribution with ex vivo MALDI-TOF mass spectrometry imaging and confocal Raman microscopy[J]. Int J Pharm, 2023, 636: 122808.
    [62] Sun SP, Tang WW, Li B. Authentication of single herbal powders enabled by microscopy-guided in situ auto-sampling combined with matrix-assisted laser desorption/ionization mass spectrometry[J]. Anal Chem, 2023, 95(19): 7512-7518.
    [63] Tang WW, Shi JJ, Liu W, et al. MALDI imaging assisted discovery of a di-O-glycosyltransferase from Platycodon grandiflorum root[J]. Angew Chem Int Ed Engl, 2023, 62(19): e202301309.
    [64] Bai HR, Wang SJ, Liu JJ, et al. Localization of ginsenosides in Panax ginseng with different age by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry imaging[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2016, 1026: 263-271.
    [65] Yang YG, Yang YB, Qiu H, et al. Localization of constituents for determining the age and parts of ginseng through ultraperfomance liquid chromatography quadrupole/time of flight-mass spectrometry combined with desorption electrospray ionization mass spectrometry imaging[J]. J Pharm Biomed Anal, 2021, 193: 113722.
    [66] Li B, Ge JY, Liu W, et al. Unveiling spatial metabolome of Paeonia suffruticosa and Paeonia lactiflora roots using MALDI MS imaging[J]. New Phytol, 2021, 231(2): 892-902.
    [67] Yamamoto K, Takahashi K, Caputi L, et al. The complexity of intercellular localisation of alkaloids revealed by single-cell metabolomics[J]. New Phytol, 2019, 224(2): 848-859.
    [68] Li B, Bhandari DR, Janfelt C, et al. Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrix-assisted laser desorption/ionization tandem mass spectrometry imaging[J]. Plant J, 2014, 80(1): 161-171.
    [69] Li B, Neumann EK, Ge JY, et al. Interrogation of spatial metabolome of Ginkgo biloba with high-resolution matrix-assisted laser desorption/ionization and laser desorption/ionization mass spectrometry imaging[J]. Plant Cell Environ, 2018, 41(11): 2693-2703.
    [70] Meng XY, Fu WQ, Huo ML, et al. In situ label-free visualization of tissue distributions of salidroside in multiple mouse organs by MALDI-MS imaging[J]. Int J Mass Spectrom, 2020, 453: 116347.
    [71] Tang WW, Chen J, Zhou J, et al. Quantitative MALDI imaging of spatial distributions and dynamic changes of tetrandrine in multiple organs of rats[J]. Theranostics, 2019, 9(4): 932-944.
    [72] Jiang HY, Gao HY, Li J, et al. Integrated spatially resolved metabolomics and network toxicology to investigate the hepatotoxicity mechanisms of component D of Polygonum multiflorum Thunb[J]. J Ethnopharmacol, 2022, 298: 115630.
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  • 收稿日期:  2023-09-18
  • 修回日期:  2023-10-27
  • 刊出日期:  2023-12-24

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