Enhanced chemodynamic therapy at weak acidic pH based on g-C3N4-supported hemin/Au nanoplatform and cell apoptosis monitoring during treatment

Abstract

Chemodynamic therapy (CDT), inducing tumor cell apoptosis through Fenton reaction to produce hydroxyl radical (·OH), is an emerging cancer treatment technology. Highly efficient Fenton catalytic reactions usually take place at a low pH environment. Utilizing graphitic carbon nitride supported hemin and Au nanoparticles (g-C₃N₄/hemin/Au) as a novel biomimetic nanocatalyst, we achieve an enhanced CDT for inducing tumor cell apoptosis in the presence of excess H₂O₂, and reveal the molecular events during the CDT-induced apoptosis. The prepared g-C₃N₄/hemin/Au nanohybrids exhibit excellent Fenton catalytic activity for the generation of highly toxic ·OH at weak acidic and neutral condition, which breaks through the limitation of traditional acidity-dependent response. The Fenton catalytic mechanism was also studied. The Fenton efficiency is primarily enhanced by the high affinity between nanohybrids and H₂O₂, and the transformation of Fe(III) to Fe(IV)=O without the formation of iron hydrate precipitation. Moreover, the intracellular molecular events during the CDT process were monitored. Phenylalanine metabolism was perturbed with protein degradation and DNA structures were damaged, which eventually lead to cell apoptosis. This study provides a significant guidance for the further development of more effective CDT platforms.

Keywords: Biomimetic nanocatalyst; Cell apoptosis monitoring; Chemodynamic therapy; Fenton catalytic activity; Hemin.