Iron Oxide Nanoparticles Carrying microRNA-124 Promote Ferroptosis in Treatment of Prostate Cancer

Prostate cancer (PCa) is a common malignancy among men worldwide. Iron oxide (Fe 3 O 4 ) nanoparticles (NPs) exhibit great potential in gene delivery and studies have noted the inhibitory effect of miR-124 on PCa cell growth. Herein, we identified the therapeutic effect of Fe 3 O 4 NPs carrying miR-124 in PCa and clarified its mechanism of action in inhibiting progression of PCa. After preparation of Fe 3 O 4 NPs carrying miR-124, human PCa cell line PC3 was treated with miR-124-Fe 3 O 4 NPs when ferroptosis inducer FIN56, ferroptosis inhibitor Liproxstatin-1, Phosphatase and tensin homolog (PTEN) inhibitor SF1670 or PTEN activator Oroxin B were added for transfection. Afterwards, assays were conducted to evaluate PCa cell biological activities. Additionally, we determined expression of PTEN and AKT and ferroptosis-related protein GPX4 and SLC7A11 in each group. We confirmed anticancer effects of miR-124-Fe 3 O 4 NPs in PCa, as they suppressed PC3 cell proliferation and migration, and induced apoptosis. Compared with miR-124-Fe 3 O 4 + Liproxstatin-1 group, the expressions of GPX4 and SLC7A11 proteins in miR-124-Fe 3 O 4 group were elevated. The advent of PTEN activator Oroxin B decreased proliferative ability of PCa cells, and SF1670 treatment decreased PTEN level and elevated AKT level. With highest apoptotic rate of PCa cells in miR-124-Fe 3 O 4 + Oroxin B + FIN56 group, intervention of SF1670 or Liproxstatin-1 changed the cell viability, while Oroxin B caused decreased AKT level and increased level of ferroptosis-related proteins. miR-124-Fe 3 O 4 NPs hinder PCa progression by promoting ferroptosis and cell apoptosis through regulation of PTEN/Akt pathway.