Porous yolk-shell Fe/Fe₃O₄ nanoparticles with controlled exposure of highly active Fe(0) for cancer therapy.

Abstract

The iron-based Fenton-type reaction has drawn tremendous attention in cancer therapy. Compared with oxidized iron, Fe(0) possesses high catalytic activity but unstable for biomedical application. Here, we report a new strategy to stabilize Fe(0) via a porous yolk shell nanostructure of Fe/Fe₃O₄ (PYSNPs) in normal physiological condition, and to control the release of Fe(0) in tumor microenvironment for enhanced cancer therapy. These PYSNPs display superior tumor inhibition with the IC₅₀ down to 20 μg/mL (over 1 mg/mL for iron oxide nanoparticles as control) for HepG2 cell. A single intravenous injection of as low as 1 mg/kg dosage is effective to suppress tumor growth in vivo. Moreover, the disintegration of PYSNPs in the acidic tumor microenvironment could cause significant change in MRI signal for contrast-enhanced diagnosis. Of note, the resulting Fe₃O₄ fragments are renal clearable with minimized side effect. In all, this work represented a nanoplatform to stabilize and selectively deliver Fe(0) for highly effective cancer therapy.