Improved Fenton Therapy Using Cancer Cell Hydrogen Peroxide*

Abstract Fenton cancer therapy as a new methodology for the treatment of tumour cells is largely restricted owing to the low stability, high aggregation, and poor selectivity of reported nanoparticles. In this study, an improved approach for the selective destruction of cancer cells is reported. Metal–organic framework (MOF) nanoparticles were synthesized and reduced via a hydrothermal method, and then PEGylated through the surface-initiated atom transfer radical polymerization (SI-ATRP) reaction to produce a PEGylated reduced MOF (P@rMOF). The ratio of PEG to nanoparticles was used to optimize the size and aggregation of the nanoparticles, with 2P@rMOF (2？:？1 mass ratio) having the smallest hydrodynamic diameter. The nanoparticles were further conjugated with folic acid for cell targeting. In？vitro cell uptake experiments demonstrated that the internalization of 2P@rMOF-FA nanoparticles into cancer cells (HeLa) was almost 3-fold that of normal cells (NIH-3T3). In the presence of 2P@rMOF-FA, the HeLa cell viability decreased dramatically to 22？%, whereas the NIH-3T3 cell viability remained higher than 80？% after 24 h incubation. The selectivity index for 2P@rMOF-FA is 4.48, which is significantly higher than those reported in the literature for similar strategies. This work thus demonstrates the most stable and selective nanoparticle system for the treatment of cancer cells using the cell’s own H2O2.