Structural engineering of magnetite nanozymes for enhanced chemodynamic cancer therapy

Abstract

Magnetite nanoparticles have demonstrated great potential as nanozymes in chemodynamic therapy (CDT) for cancer. However, their in vivo efficiency remains limited. Here we developed magnetite nanozymes (MNZs) with dual enzyme activities and demonstrated their shape-dependent behavior in eradicating tumors. Three versions of MNZs were constructed of the same materials but largely different geometric forms: spherical (SMNZ), elliptic (EMNZ) and flaky (FMNZ); they were evaluated against each other in treating an aggressive mouse tumor model of triple-negative breast cancer. We showed that the shape influence is substantial, and with the optimal geometric form, FMNZ dramatically outperform its two counterparts and demonstrates phenomenal ability to shrink tumors via systemic injection. We further illustrated that the vastly increased treatment efficiency can be attributed to the large surface area of FMNZ that resulted in increased cellular uptake, greater iron ions release and increased production of highly toxic hydroxyl radicals (•OH), which leads to enhanced self-cascade CDT.