Oil‐Coated Nanoplastics Induce Rapid Membrane Disruption and Severe Intestinal Injury

Plastic food containers used in food delivery may pose underrecognized health risks by releasing micro- and nanoplastics (MNPs), especially when in contact with oil-rich foods. Here, we show that cooking oil dramatically increased MNP release from polypropylene (PP) and polyethylene (PE)-coated containers within 3 min of microwave heating, reaching up to 1.52 × 10¹⁴ particles/L, approximately 125-fold higher than with water. Concurrently, the co-release of plastic additives and heavy metals increased by up to 309-fold. Soybean oil-derived PP nanoplastics were four times more cytotoxic (IC₅₀ = 18.7 µg/mL) than water-derived particles (IC₅₀ = 77.1 µg/mL), likely due to oil-film coatings, a positive surface charge (+7.37 mV), altered surface properties, and co-extracted additives. Fluorescence and transmission electron microscopy revealed rapid membrane disruption within 5 min of exposure at 100 µg/mL. In vivo, oral exposure of mice to oil-derived nanoplastics (50 mg/kg) for two weeks caused severe intestinal barrier damage and mucosal immune dysfunction. These adverse effects were partially alleviated by Immune- and barrier-targeted interventions. Benchmark dose modeling established safety thresholds of 0.4 µg/mL at the molecular level and 15.83 mg/kg for tissue injury. Alarmingly, modeled five-year gastrointestinal burdens and reported human tissue MNP levels exceeded molecular safety thresholds by up to 1107-fold, though not tissue injury thresholds. These findings highlight the urgent need for stricter regulations on oil-contact plastics and the development of safer food packaging materials.