AbstractBackground & AimsHepatocellular carcinoma (HCC) is associated with a poor prognosis because of a lack of effective treatment options. The objective of this study was to examine a new strategy for HCC treatment, namely the use of poly (ADP‐ribose) polymerase 1 (PARP‐1) inhibitor (ABT‐888) together with Temozolomide (TMZ) incorporated onto magnetic nanoparticles.MethodsMagnetic Fe3O4/Fe cores were encapsulated within a silica shell to facilitate the simultaneous incorporation of ABT‐888 and TMZ. In vitro tests were performed with HepG2, Hep3B and PLC‐PRF‐5 liver tumoural cell lines and with WRL‐68 liver non‐tumoural cells.ResultsThe magnetic nanocarriers were loaded simultaneously with ABT‐888 and TMZ. High stability and extended release were achieved in culture medium. Confocal microscopy images showed that drug‐loaded particles were uptaken and accumulated into the cytoplasm of liver tumoural cells, inducing the following effects: G2/M cell cycle arrest (P < 0.05), accumulation of DNA damage (P < 0.05), mitochondrial depolarization (P < 0.01), reduction in BCL‐xL, FOS, JUND gene expression (P < 0.05), PARP‐1 fragmentation, Caspase‐3 activation and apoptotic cell death (P < 0.05). Interestingly, drugs loaded onto nanoparticles exhibited better efficiency than free drugs (cell death triggered by drug delivery nanosystem: 53.5% vs. 34.5% by free drugs, P = 0.01).ConclusionsThese magnetic nanocompounds are able to incorporate both drugs simultaneously, enter the tumour cells and release them. ABT‐888/TMZ/NPs decrease the transcription of key genes involved in tumour survival and induce apoptotic cell death in a more effective manner than is achieved by free drugs.