Small Organic Catalase Mimic Encapsulated in Micellar Artificial Organelles as Reactive Oxygen Species Scavengers AITranslate

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DOI：https://doi.org/10.1021/acsapm.9b00308

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Biocatalytic intracellular active nanoreactors (artificial organelles) aim to support their host cells. Here, we report the first successful micelle-based artificial organelles containing a salen–manganese complex (EUK) as catalase mimic with intracellular activity in HepG2 cells to act as reactive oxygen species (ROS) scavengers. Four different EUKs were synthesized and compared in their ability to convert hydrogen peroxide to water and oxygen as free compounds and when encapsulated into micelles assembled from the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-(dimethylamino)ethyl methacrylate). An EUK candidate with an asymmetric substitution of chemical groups at the ortho and the meta position (EUK-B) was identified as lead candidate. HepG2 cells continued proliferating when preincubated with low concentrations of EUK-B-containing micelles (MB). Importantly, HepG2 cells equipped with MB showed improved viability compared to the controls when stressed with paraquat, a compound that induces ROS generation. The intracellular activity of MB was supported by lower amounts of intracellular detectable ROS. This first report on the combination of artificial enzymes and artificial organelles further extends the opportunities in therapeutic cell mimicry.