Calcium phosphate nanoparticles efficiently deliver miR-205-5p to modulate oncogenic targets in prostate cancer cells.

Prostate cancer (PCa) at the bone metastatic stage remains a global health challenge with low survival rates. This study aimed to identify therapeutic microRNAs (miRNAs) for delivery by calcium phosphate nanoparticles (CaP-NPs) to modify transcript profiles in PCa. Microarray analysis identified miR-205-5p as differentially downregulated in PCa bone metastatic cells (PC-3). CaP-NPs containing mimetic molecules of miR-205-5p were successfully prepared. Particles were spherical, sterile, and homogeneous and measured approximately 50 nm. CaP-NPs efficiently delivered miR-205-5p to cells, restoring its expression and inducing cell death. Transcript levels of the target genes AR, BAMBI, SMAD1/5/9, VEGFA, and ZEB1 decreased following miR-205-5p delivery. Live-cell imaging demonstrated the uptake of CaP-NPs in both two-dimensional (PC3-cells monolayer culture) and three-dimensional (C4-2B-derived microtumor) cancer models. The three-dimensional model was produced in a microwell system inoculated with C4-2B cells, which readily form microtumors resembling disseminated PCa cells. Collectively, these results confirm miR-205-5p as a tumor suppressor in bone metastatic PCa cells and suggest that CaP-NPs could be a promising delivery system for further preclinical exploration in gene therapy targeting bone metastatic PCa.