Smart Fluorescence-Responsive Polymer Hybrid Nanoparticles for Ferroptosis-Associated Therapy and Pathological Ion Detection in OSCC Cells.

Oral squamous cell carcinoma (OSCC) remains a challenging malignancy due to poor drug efficacy and adverse effects. Resveratrol (RV) shows anti-OSCC potential but suffers from low solubility and bioavailability. To address this, a multifunctional polymer hybrid nanoparticle-poly(lactic-co-glycolic acid) (PLGA) modified with compound 1 and 4-(trimethoxysilyl)butanoic acid (TMSBA), and co-loaded with compound 2 and resveratrol (RV) (1-PLGA-TMSBA@2@RV)-was developed for fluorescence-responsive ferroptosis-associated therapy and pathological ion detection. The material exhibited high fluorescence selectivity toward OSCC-related GSH⁻ and Fe³⁺ ions, with quenching efficiencies of 98% and 92.9%, and a GSH⁻ detection range of 10⁻⁷-10⁻² M (R² = 0.9944) and Fe³⁺ detection limit of 10⁻⁶ M. CCK-8 assays showed RV-NPs significantly inhibited CAL-27 cell proliferation, outperforming free RV (53.8%), with blank carriers demonstrating good biocompatibility. qRT-PCR revealed RV-NPs downregulated ferroptosis regulator SLC7A11 by 71.2%, suggesting a ferroptosis-mediated antitumor mechanism. This nanoplatform offers an integrated approach for enhanced OSCC therapy and real-time pathological ion detection.