Abstract
Inflammation is associated with many diseases, in which activated inflammatory cells produce various reactive oxygen species (ROS), including H 2 O 2 . This work proposes an ultrasensitive ROS-responsive hollow microsphere (HM) carrier that contains an anti-inflammatory drug, an acid precursor consisting of ethanol and FeCl 2 , and sodium bicarbonate (SBC) as a bubble-generating agent. In cases of inflamed osteoarthritis, the H 2 O 2 at low concentration diffuses through the HMs to oxidize their encapsulated ethanol in the presence of Fe 2+ by the Fenton reaction, establishing an acidic milieu. In acid, SBC decomposes to form CO 2 bubbles, disrupting the shell wall of the HMs and releasing the anti-inflammatory drug to the problematic site, eventually protecting against joint destruction. These results reveal that the proposed HMs may uniquely exploit biologically relevant concentrations of H 2 O 2 and thus be used for the site-specific delivery of therapeutics in inflamed tissues.