Targeting of Hypoxia in AQ4N-treated Tumour Xenografts by MALDIIon Mobility Separation-Mass Spectrometry Imaging

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Abstract
Abstract: Hypoxia is a common feature observed in solid tumours. It is a target of interest in oncology as it has been found to be closely associated with tumour progression, metastasis and aggressiveness and confers resistance to a variety of chemotherapeutic agents as well as radiotherapy. AQ4N, also known as banoxatrone or 1,4-bis-[2-(dimethylamino-Noxide) ethyl]amino-5,8-dihydroxyanthracene-9,10-dione is a very promising bioreductive prodrug. This paper, describes an application of MALDI-MSI combined with ion mobility separation and an "on-tissue" bottom up proteomic strategy to obtain proteomic data from AQ4N dosed tumour xenograft tissue sections. These data are then correlated with the drug distribution determined also using MALDI-ion mobility separation-mass spectrometry imaging (MALDI-IMS-MSI). PCA-DA and OPLS-DA have been used to compare treated and untreated xenografts and of note is the marked increase in expression of Histone H3.