AB025. The effects and mechanisms of magnetic nanomaterials in prostate cancer diagnosis and therapy

Background: Take iron oxides (Fe₃O₄) nanoclusters for instance, to explore the effects and mechanisms of magnetic nanomaterials in prostate cancer diagnosis and therapy.

Methods: Fe₃O₄ nanoclusters (Fe₃O₄ NCs) were synthesized by using hydrothermal method through iron (III) acetylacetonate. The as-prepared Fe₃O₄ NCs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The T₂-weighted image was obtained with a 3.0 T clinical MRI scanner. To establishing PC3-GFP-LC3, a PC3 cell line stably expressing green-fluorescent-protein-tagged microtubule-associated protein 1 light chain 3 (GFP-MAP1LC3), and then evaluate the effect of Fe₃O₄ NCs upon cell proliferation. To use 4 W/cm² near infrared laser (NIR, 808 nm), the light-thermal conversion of Fe₃O₄ NCs was assessed. GFP-LC3 punctate dots were observed by an invert microscope and LC3-I/LC3-II conversion was detected by western blotting. Autophagosome formation was observed by TEM. The tumoricidal effects to PC3 were evaluated by cell proliferation assay in vitro and xenograft volume curve in vivo under NIR in the presence or absence of autophagy inhibitors.

Results: The as-prepared hydrophilic and magnetic Fe₃O₄ NCs were 100 nm in uniform size. XRD and FTIR analyses showed the NCs possessed the characterized peak and functional motifs, r₂ value could reach 143 mM^-1S^-1, after magnetic targeting, the r₂ value could further shorten. Fe₃O₄ NCs did not affect the cell proliferation at 0–400 µg/mL, indicating the good biocompatibility. Fe₃O₄ NCs could induce the medium temperature elevated in a time- and dose-dependent manner under 808 nm NIR irradiation. Besides, Fe₃O₄ NCs could induce complete autophagic flux in PC3 cells, which effect could be inhibited by 3-MA or CQ administration. Under 808 nm NIR, Fe₃O₄ NCs could elicit 40% cell viability reduction, this reduction could be further enhanced when co-treated with 3-MA or CQ. In vivo study showed that under 808 nm NIR, tumor volume in NS, 3-MA, CQ group increased with prolonged time, while Fe₃O₄ NCs administration could inhibit the volume increase, when 3-MA or CQ was administrated simultaneously, the tumor volume was sustained with the initial treatments, the body weight of mice in each group did not alter significantly.

Conclusions: Fe₃O₄ NCs are safe T₂-MRI contrast nano-contrast agents, could enhance the sensitivity of prostate cancer diagnosis. The NCs possess outstanding light-thermal conversion capacity, could induce autophagy in PC3 cells. More importantly, Fe₃O₄ NCs could further enhance the tumoricidal effects under 808 nm NIR when the autophagiy-inducing effects are inhibited in PC3 cells.

Keywords: Magnetic nanomaterials; prostate cancer; diagnosis and therapy