Monolayer protected gold nanoparticles (MPGN) coated with metal chelating groups were prepared. In the presence of Ce(IV), the MPGN proved to be highly active in promoting the hydrolytic cleavage of the DNA model bis-p-nitrophenyl phosphate (BNP). A 2.5 million-fold rate acceleration of the BNP hydrolysis was measured at a concentration of Ce(IV) as low as 120 μM (pH 7, 25 °C). This corresponds to a reduction of the substrate half-life time from 2000 years to few hours. The MPGN-Ce(IV) system is 1 to 2 orders of magnitude more reactive than any mono- and binuclear Ce(IV) complex so far reported. The source of such reactivity is the cooperation between the metal ions self-organized on the surface of the nanoparticles.