ROS-activated oral enterosorbent nanogel to block gastrointestinal absorption of lead and cadmium: an <i>in vitro</i> study

Occupational ingestion of metal-laden dust in quarry and mining environments contributes significantly to chronic exposure to lead (Pb) and cadmium (Cd). In the present study, we developed a non-systemic oral enterosorbent nanogel incorporating reactive oxygen species (ROS)-activated pro-chelators. The thiol-based metal-binding motifs were protected using aryl-boronate groups and selectively deprotected in the presence of hydrogen peroxide (H₂O₂), generating high-affinity thiol sites capable of binding Pb²⁺ and Cd²⁺ while minimizing interaction with essential divalent ions. Adsorption performance was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). ROS activation accelerated thiol exposure (t₁/₂ = 18-40 min) and significantly enhanced adsorption capacity, reaching Qmax values of approximately 60 mg g^-1 for Pb²⁺ and 40 mg g^-1 for Cd²⁺. The activated nanogel demonstrated preferential binding toward toxic metals over competing ions, including Zn²⁺, Ca²⁺, and Mg²⁺, and maintained ≥80% adsorption performance after five adsorption-desorption cycles. These findings provide an <i>in vitro</i> proof-of-concept for a ROS-activated oral enterosorbent capable of selectively sequestering toxic metals in gastrointestinal environments, with potential application in reducing gastrointestinal bioavailability following occupational exposure.