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

Chemodynamic therapy (CDT), inducing tumor cell apoptosis through Fenton reaction to produce hydroxyl radical (center dot 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 center dot 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.

Automated summary

Chemodynamic therapy (CDT) induces tumor cell apoptosis through Fenton reaction, with the use of graphitic carbon nitride supported hemin and Au nanoparticles enhancing CDT efficacy by generating highly toxic hydroxyl radicals under neutral conditions. The Fenton catalytic mechanism is primarily enhanced by the high affinity between nanohybrids and H2O2, resulting in cell apoptosis through perturbations in phenylalanine metabolism, protein degradation, and DNA damage. This study offers significant insights for the development of improved CDT platforms.