An increasing number of studies have reported the use of various nanoparticles to encapsulate cisplatin, a frontline chemotherapeutic drug against a broad-spectrum of cancers, for overcoming its inherent drawbacks in clinical applications. Nevertheless, few analytical methods or instruments could provide the precise distribution information on this platinum drug in biological tissues. Herein, we provide the first evidence of applying matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to assess the spatial distribution of cisplatin released from the cell-penetrating poly(disulfide) (CPD)-modified hollow iron oxide nanoparticles (hFe3O4-MPS-CPD) at the kidneys via an in situ glutathione (GSH) responsive mode. The cisplatin released from the nanoparticles triggered by GSH was successfully examined as [Pt(DDTC)2]+ (m/z 491.01) and [Pt(DDTC)3]+ (m/z 639.04) by MALDI-MS after derivatization using diethyldithiocarbamate. The in situ spatial distribution of [Pt(DDTC)2]+ and [Pt(DDTC)3]+ in the kidneys was then mapped using MALDI-MSI. This study presents an optimized analytical approach to evaluate and map the metallodrug in biological tissue samples in an efficient and convenient manner, offering great assistance in investigating the biodistribution of cisplatin delivered by nanoparticles, and sheds light on facilitating the studies of the pharmacokinetics of cisplatin in biomedical research.
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