pH-responsive iron-loaded carbonaceous nanoparticles for chemodynamic therapy based on the Fenton reaction

The Fenton reaction-based chemodynamic therapy is a form of cancer therapy, and its efficacy can be significantly improved by promoting catalytic reactions involving iron ions. A system with high catalytic capacity and low biological toxicity that effectively inhibits tumor progression is required for optimal treatment. In this study, iron-loaded carbonaceous nanoparticles (CNPs@Fe) with Fenton catalytic activity were fabricated and applied for the chemodynamic therapy of cancer. The carbonaceous nanoparticles derived from glucose via a caramelization reaction demonstrated high biocompatibility. Besides, aromatic structures in the carbonaceous nanoparticles helped accelerate electron transfer to enhance the catalytic decomposition of H₂O₂, resulting in the formation of highly reactive hydroxyl radicals (˙OH). At pH 6.0 (representing weak acidity in the tumor microenvironment), the Fenton catalytic activity of CNPs@Fe in the decomposition of H₂O₂ was 15.3 times higher than that of Fe²⁺ and 28.3 times higher than that of Fe₃O₄via a chromogenic reaction. The reasons for the enhancement were revealed by analyzing the chemical composition of carbonaceous nanoparticles using high-resolution mass spectra. The developed Fenton agent also demonstrated significant therapeutic effectiveness and minimal side effects in in vitro and in vivo anticancer studies. This work proposes a novel approach to promote the generation of reactive oxygen species (ROS) for the chemodynamic therapy of cancer.