286 - Pegylated manganese protoporphyrin self-assembles into nanoparticles in aqueous media and exerts potent catalase-mimic activity to protect oxidative cellular damages

Abstract

Certain types of metalloporphyrin derivatives have been studied their therapeutic potentials against oxidative stress related diseases according to their catalase-mimic activities. Here we describe the synthesis, physicochemical properties, and catalase-like activity of polyethylene glycol (PEG) conjugated manganese protoporphyrin (PEG-MnPP). Carboxyl groups of protoporphyrin ring at C6 and C7 positions were first activated by ethyl chloroformate, followed by reacting with tert-butoxycarbonyl (Boc)-ethylenediamine. Boc moieties were then removed to introduce amino groups onto protoporphyrin structure. To the amino groups were conjugated with succinimidyl PEG having average molecular weight of 2000 to obtain pegylated protoporphyrin (PEG-PP). Manganese was chelated into protoporphyrin ring to synthesize PEG-MnPP by incubating PEG-PP and manganese acetate in methanol. PEG-MnPP was highly water-soluble; the saturated concentration of PEG-MnPP in water was determined to be approximately 3 mM. Dynamic light scattering and fluorescent spectrometry analyses revealed that PEG-MnPP self-assembled into nanoparticles with micelle-like structure consisting of hydrophobic MnPP core surrounded by hydrophilic PEG chains in aqueous media having apparent molecular size of 400 nm in a diameter. PEG-MnPP can effectively eliminate hydrogen peroxide from culture media and protected mammalian cultured cells from toxic insults induced by hydrogen peroxide exposure. Intravenous administration of PEG-MnPP reduced liver injury of mice treated with acetaminophen. These data warrant further study to explore therapeutic potential of PEG-MnPP as water-soluble metalloporphyrin-based catalase mimic to oxidative stress associated diseases.