In vivo effects of Cisplatin and titanium dioxide nanoparticles combined treatment

Abstract

Cisplatin, the first metal-based chemotherapeutic drug, remains widely used despite its toxicity. Combining cisplatin with nanoparticles has been proposed to improve its therapeutic profile, although most studies rely on in vitro models. Using RNA-seq and bioinformatic analyses, we investigated the in vivo transcriptional effects of cisplatin (50 g/ml) and titanium dioxide nanoparticles (TiO2 NPs; 50 g/ml), alone and in combination, in Drosophila melanogaster. Flies exposed to cisplatin or TiO2 NPs alone exhibited modulation of genes associated with xenobiotic metabolism and detoxification. In contrast, combined exposure resulted in a markedly reduced number of upregulated differentially expressed genes (DEGs):CG10013, aqz, CG5568, and CG3213, which are related to cell division and DNA/RNA metabolism, likely due to a synergistic effect of the cisplatin and TiO2 administered simultaneously. We also observed that combined exposure promotes downregulation of genes involved in xenobiotic metabolism, detoxification, innate immune collapse, and reproduction and fertility. Although mortality rates were not significantly affected in any group, flies from the CIS/NPTIO2 group exhibited impaired climbing performance. These results suggest that co-exposure to cisplatin and TiO2 nanoparticles induces transcriptional suppression, potentially impairing essential cellular processes.