Reactive oxygen species (ROS) are important factors in many clinical diseases. However, direct delivery of antioxidant enzymes into cells is difficult due to poor cell uptake. A proper design of delivery of enzymes by nanoparticles is very desirable for therapeutic purposes. To overcome the cell barrier problem, a designed mesoporous silica nanoparticle (MSN) system with attached TAT-fusion denatured enzyme for enhancing cell membrane penetration has been developed. Simultaneous delivery of two up-downstream antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase(GPx), reveals synergistic efficiency of ROS scavenging, compared to single antioxidant enzyme delivery. TAT peptide conjugation provided a facile nonendocytosis cell uptake and escape from endosome while moving and aggregating along the cytoskeleton that would allow them to be close to each other at the same time, resulting in the cellular antioxidation cascade reaction. The two-enzyme delivery shows a significant synergistic effect for protecting cells against ROS-induced cell damage and cell cycle arrest. The nanocarrier strategy for enzyme delivery demonstrates that intracellular anti-ROS cascade reactions could be regulated by multifunctional MSNs carrying image fluorophore and relevant antioxidation enzymes.
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