Abstract
Prostate cancer (PCa) presents a formidable therapeutic challenge owing to the limited efficacy of existing treatments. In this study, a series of comparative experiments demonstrated that nanodiamonds (NDs) with different functional groups exhibit inhibitory effects on the growth, replication, and migration of prostate cancer cells without directly killing the cells. Among them, aminated nanodiamonds (aNDs) showed the most pronounced inhibitory activity. Subsequently, a combination of proteomics analysis and machine learning was employed to elucidate the molecular mechanisms by which these aNDs exerted their inhibitory effects on PCa progression. Data-independent acquisition proteomics identified the key proteins affected by the aNDs, and the Kyoto Encyclopedia of Genes and Genomes analysis revealed ribosome pathway enrichment. Bioinformatics analysis focused on ten crucial genes, thus incorporating a novel prognostic model that categorized patients based on gene expression and emphasized the significance of mitochondrial ribosomal protein L22 (MRPL22). In vivo experiments confirmed the antitumor effects and biocompatibility of the aNDs. In addition, an analysis of the response of MRPL22 to anticancer drugs in public databases revealed its relevance to a range of drugs and compounds. In summary, this study integrated diverse interdisciplinary methodologies, thereby offering insights into the mechanism of the inhibition of PCa by the aNDs and the regulatory role of MRPL22 in the ribosomal pathway.