Catalase-Modulated Heterogeneous Fenton Reaction for Selective Cancer Cell Eradication: SnFe₂O₄ Nanocrystals as an Effective Reagent for Treating Lung Cancer Cells

Abstract

Heterogeneous Fenton reactions have been proven to be an effective and promising selective cancer cell treatment method. The key working mechanism for this method to achieve the critical therapeutic selectivity however remains unclear. In this study, we proposed and demonstrated for the first time the critical role played by catalase in realizing the therapeutic selectivity for the heterogeneous Fenton reaction-driven cancer cell treatment. The heterogeneous Fenton reaction, with the lattice ferric ions of the solid catalyst capable of converting HO to highly reactive hydroxyl radicals, can effectively eradicate cancer cells. In this study, SnFeO nanocrystals, a recently discovered outstanding heterogeneous Fenton catalyst, were applied for selective killing of lung cancer cells. The SnFeO nanocrystals, internalized into the cancer cells, can effectively convert endogenous HO into highly reactive hydroxyl radicals to invoke an intensive cytotoxic effect on the cancer cells. On the other hand, catalase, present at a significantly higher concentration in normal cells than in cancer cells, remarkably can impede the apoptotic cell death induced by the internalized SnFeO nanocrystals. According to the results obtained from the in vitro cytotoxicity study, the relevant oxidative attacks were effectively suppressed by the presence of normal physiological levels of catalase. The SnFeO nanocrystals were thus proved to effect apoptotic cancer cell death through the heterogeneous Fenton reaction and were benign to cells possessing normal physiological levels of catalase. The catalase modulation of the involved heterogeneous Fenton reaction plays the key role in achieving selective cancer cell eradication for the heterogeneous Fenton reaction-driven cancer cell treatment.

Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions

“…[29] Fori nstance,o ur group synthesized amorphous Fe 0 nanoparticles (AFeNPs) (Figure 1a), [25] which were rapidly ionized in an acidic TME to release more Fe 2+ ions than Fe 0 nanocrystals (FeNCs) for CDT because it had the reactive nature of metallic glasses.A sp resented in Figure 1b,c, the release rate of ferrous ions from the AFeNPs reached 57 %at ap Ho f6 .5 and 100 %a tapH of 5.4 within 6h,w hich were much higher than those observed for the FeNCs.M oreover, both AFeNPs and FeNCs tended to slowly release ferrous ions at aneutral pH. These results confirmed the capacity of AFeNPs for selective ferrous ion release,t hus ensuring the efficiency of CDT.I na ddition, many other iron-based nanomaterials,i ncluding Fe oxides, [30][31][32] [FeO(OH) n ], [33] and M(Sn,Mn)Fe 2 O 4 [34,35] have also been introduced as CDT agents,b ut none have focused on increasing the release of the catalytic Fe 2+ ions.…”

Iron Chelators and Exogenic Photosensitizers. Synergy through Oxidative Stress Gene Expression

“…However higher level of H 2 O 2 may also facilitate the Fenton reaction generating more ROS and leading to the cell death. Thus lowering the CAT expression may increase effectivity of TSC therapy 36 . On the other hand higher CAT activity produce more oxygen which may enhance the PDT process as recently reported by Min et al 37 .…”

Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions

“…These results confirmed the capacity of AFeNPs for selective ferrous ion release, thus ensuring the efficiency of CDT. In addition, many other iron‐based nanomaterials, including Fe oxides, [FeO(OH) n ], and M(Sn,Mn)Fe 2 O 4 have also been introduced as CDT agents, but none have focused on increasing the release of the catalytic Fe 2+ ions.…”