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 and the emergence of drug resistance. Combining cisplatin with nanoparticles has been proposed to improve its therapeutic profile, although most studies rely on in vitro models. Here, we investigated the in vivo transcriptional effects of cisplatin (50 μg/ml) and titanium dioxide nanoparticles (TiO□ NPs; 50 μg/ml), alone and in combination, in Drosophila melanogaster . Using RNA-seq and bioinformatic analyses, we assessed differential gene expression across treatments. Flies exposed to cisplatin or TiO□ 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. Also, we observed that the combined exposure promotes the downregulation of DEGs involved in xenobiotic metabolism, detoxification, collapse of the innate immune system, and reproductive impairment and fertility. Mortality rates were not significantly affected in any group. These results suggest that co-exposure to cisplatin and TiO□ nanoparticles induces a global transcriptional suppression, potentially impairing essential cellular processes.