Scheme 1
Schematic illustration showing Abplatin(IV) inhibited the tumor growth on a patient-derived tumor xenograft model of hepatocellular carcinoma (PDXHCC) and its comparative multi-omics study with cisplatin. A Abplatin(IV) was prepared by the physical encapsulation of a hydrophobic CisPt(IV) with HSA. B Subsequently, Abplatin(IV) was intraveneously (i.v.) injected into the mice bearing PDXHCC. Abplatin(IV) could be accumulated at the tumor site via blood circulation and internalized by the cancer cells via endocytosis. C The possible mechanism of Cisplatin (Left panel) and Abplatin(IV) (Right panel). The Pt(II) in cisplatin might directly bind to DNA to cause cell apoptosis. However, Abplatin(IV) was believed to be reduced by intracellular reducing agents such as glutathione(GSH) and ascorbic acid to release Pt(II) for DNA binding. Transcriptomics and metabolomics study on the mechanism of Abplatin(IV) revealed Abplatin(IV) significantly disturbed the purine metabolism pathway. Up-regulated and down-regulated metabolites were represented in red and blue, respectively. Lipidomics study showed that Abplatin(IV) induced the disorder of glycerophospholipids and sphingolipids