Aging-related diseases such as Alzheimer’s and osteoarthritis are characterized by the presence of elevated cholinergic enzyme acetylcholineesterase (AChE) and overexpressed reactive oxygen species (ROS). These overexpressed biomarkers cause damage ...
Aging-related diseases such as Alzheimer’s and osteoarthritis are characterized by the presence of elevated cholinergic enzyme acetylcholineesterase (AChE) and overexpressed reactive oxygen species (ROS). These overexpressed biomarkers cause damage to nervous synapses in the autonomic nervous system responsible for movement and cause progression of degeneration of joints and other body parts. Herein, we designed stimuli-responsive electrochemical hydrogel sensors by coupling polymer dots with hydrogel matrices for targeting acetylcholinesterase in Alzheimer's disease and reactive oxygen species in osteoarthritis. For Alzheimer’s disease, we synthesized an AChE-responsive, dual-mode (fluorescent and electrochemical) biosensor by loading acetylthiocholine (ATCh) and a diselenide- crosslinked polymer dot-polydopamine complex (PDA@dsPD) into the hydrogel matrix. When AChE hydrolyzed ATCh to thiocholine (TCh), TCh cleaved diselenide bonds, leading to fluorescence dequenching and impedance modulation, which enabled sensitive readout of both AChE activity and its inhibition. For aging-related diagnosis, we fabricated a ROS-responsive (PD/MnO₂) hydrogel, in which cellular ROS reduce MnO₂ to Mn²⁺, concomitantly shifting fluorescence and electrochemical impedance. The sensor produced consistent signals in chondrocyte senescence models—serial passaging and PPARα siRNA knockdown—and simultaneously exerted ROS-scavenging effects that helped rebalance redox status. In summary, these touch-operable, dual-mode hydrogel sensors discriminate AChE activity/inhibition and ROS-driven cellular senescence while offering adjunctive theranostic benefits via ROS scavenging.