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.

化学动力疗法（CDT）通过Fenton反应诱导肿瘤细胞凋亡以产生羟基自由基（·OH），是一种新兴的癌症治疗技术。高效的Fenton催化反应通常在低pH环境下进行。利用石墨化碳氮化物负载的血红素和金纳米粒子（gC ₃ N ₄ / hemin / Au）作为新型仿生纳米催化剂，我们获得了增强的CDT，可在过量H ₂ O ₂存在下诱导肿瘤细胞凋亡，并揭示分子事件在CDT诱导的细胞凋亡过程中。制备的gC ₃ N ₄/ hemin / Au纳米杂化物在弱酸性和中性条件下表现出出色的Fenton催化活性，可产生高毒性的·OH，从而突破了传统酸度依赖性反应的局限性。还研究了芬顿催化机理。Fenton效率主要通过纳米杂化物与H ₂ O ₂之间的高亲和力以及从Fe（III）到Fe（IV）= O的转化而不会形成铁水合物沉淀来提高。此外，监测了CDT过程中的细胞内分子事件。苯丙氨酸代谢受到蛋白质降解的干扰，DNA结构被破坏，最终导致细胞凋亡。这项研究为进一步开发更有效的CDT平台提供了重要指导。