Abstract
Reactive oxygen species (ROS) secreted by activated macrophages play a central role in causing rheumatoid arthritis, and therapeutics that can inhibit the production of ROS by macrophages have great clinical potential. Superoxide dismutase (SOD) and catalase (CAT) are two enzymes that scavenge ROS and have great potential for treating rheumatoid arthritis. However, clinical trials with these enzymes have been ineffective, due to drug delivery problems, and effective SOD and CAT delivery vehicles are greatly needed. In this communication, we demonstrate that CAT and SOD can be effectively targeted to activated macrophages, via the folate receptor. Folate was conjugated to CAT and SOD using NHS/EDC chemistry with high efficiency. Cell culture experiments demonstrated that folate conjugation increased their ability to scavenge ROS, produced by the macrophages, and also enhanced their uptake into activated macrophages. We anticipate numerous applications of folate-conjugated CAT and SOD in treating inflammatory diseases, based on their efficacy and straightforward synthesis.
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