Fe ₃ O ₄ @Au loaded with PNPO-siRNA for the diagnosis and treatment of ovarian cancer

Aim To design and fabricate composite magnetic nanoparticles (MNPs), Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA, for the diagnosis and treatment of ovarian cancer (adenocarcinoma cells).Materials and methods Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles were synthesized using seed growth and chemical reduction methods. The fabricated Fe3O4@Au nanoparticles were systematically characterized and evaluated. For in vitro studies, the anti-tumor effects were assessed in naturally resistant SKOV3 ovarian adenocarcinoma cells. Cellular uptake, gene-silencing efficiency, and cytotoxicity assays were conducted to determine their therapeutic potential. For in vivo studies, a xenograft mouse model harboring SKOV3 tumors was established to evaluate magnetic resonance imaging (MRI) contrast enhancement and biosafety of nanoparticles. MRI was performed using T2-weighted imaging (T2WI) to monitor tumor accumulation and signal changes. The biosafety was further examined through histopathological analysis of major organs.Results We successfully designed and fabricated Fe3O4@Au composite magnetic nanoparticles (MNPs) encapsulated with surface lipids, which exhibited excellent biocompatibility and safety. These Fe3O4@Au composite MNPs effectively delivered PNPO-siRNA into SKOV3 cells, enabling both ovarian cancer treatment and MRI. In vivo MRI of SKOV3 tumor-bearing mice showed effective tumor accumulation of nanoparticles. T2WI revealed a peak signal reduction of approximately 17% at 3h post-injection (ANOVA, compared to the pre-injection group, ***p < 0.001), followed by gradual recovery over time. These findings indicate that Fe3O4@Au MNP can serve as effective negative MRI contrast agent to enhance ovarian cancer detection. For therapeutic evaluation, Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles significantly inhibited SKOV3 cell proliferation in vitro. Furthermore, biosafety assessments demonstrated no significant toxicity in major organs, supporting their potential for as a safe and effective platform for the treatment of ovarian cancer.Conclusion Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA composite magnetic MNPs demonstrate significant potential as dual-function agents, serving both as MRI tracers and as molecular therapeutic platforms for ovarian cancer in vivo.