Fenton‑Engineered Sporopollenin With In Vivo Interfacial Targeting for Gut Microenvironment‑Synergized Clearance of 4‑Ethylphenol, an Autism‑Related Metabolite

ABSTRACT Targeted clearance of gut‑derived hydrophobic metabolites such as 4‑ethylphenol (4‑EP) offers a potential therapeutic route for autism spectrum disorder (ASD) via the gut–brain axis. However, 4‑EP tends to accumulate at dietary lipid–water interfaces, which are poorly accessible to conventional oral adsorbents that rely on passive diffusion. To address this issue, we engineered Fenton‑modified sporopollenin microparticles (Ft‑SFs) for active interfacial targeting. Ft‑SFs exhibit superhydrophobicity (contact angle 152.8°) that enables spontaneous anchoring at oil–water interfaces, and a hierarchical porous structure that facilitates high‑capacity capture. In simulated intestinal fluid, Ft‑SFs synergize with bile salts and trypsin to achieve an adsorption capacity of 117.86 mg g − 1 and a removal efficiency of 94.35%. In vivo fluorescence imaging confirmed intestinal targeting and prolonged retention (69.42% ex vivo adhesion at 4 h), together with favorable biocompatibility. These findings demonstrate that Ft‐SFs represent a promising oral adsorbent for 4‑EP clearance, and the interfacial targeting strategy provides a feasible approach for removing gut‑derived metabolites.