Smart Oral Capsule with a Closed-Loop Sense–Decide–Act Strategy for Colitis Therapy

Current treatments for inflammatory bowel disease (IBD) lack real-time inflammatory monitoring and lesion-specific drug delivery, resulting in poor efficacy and systemic toxicity. To address this, we present a smart oral capsule that operates a closed-loop “sense–decide–act” strategy entirely autonomously—sensing and drug release are driven by changes in the digestive tract environment without any external intervention. The capsule features a dual-layer shell sequentially responsive to pH and matrix metalloproteinases (MMPs), enabling colon-targeted delivery and inflammation-specific activation. An integrated multimodal sensor wirelessly tracks colonic TNF-α (>5 ng mL–1), pH (>7.0), and Na+ (>100 mM). The encapsulated budesonide nanoparticles (Bud@PEG-SS-NPs) release the drug specifically in reactive oxygen species (ROS)-rich microenvironments and show superior anti-inflammatory efficacy in both lipopolysaccharide (LPS)-induced cellular models and dextran sulfate sodium (DSS)-induced mouse colitis. In live rats, the capsule achieved on-demand drug release in response to elevated local TNF-α levels, and a single intervention significantly alleviated inflammation. This work establishes a new paradigm for personalized, adaptive IBD therapy and provides a versatile platform for closed-loop management of other gastrointestinal diseases.