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Smart Fluorescence-Responsive Polymer Hybrid Nanoparticles for Ferroptosis-Associated Therapy and Pathological Ion
Shujuan Yu1, Feng Chen2, Leidi Yuan3
1Department of Stomatology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China.
Abstract:
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.
Insights
This study developed novel nanoparticles for oral cancer therapy. These nanoparticles enhance resveratrol
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
- Molecular Diagnostics
Background:
- Oral squamous cell carcinoma (OSCC) presents therapeutic challenges due to limited drug effectiveness and side effects.
- Resveratrol (RV) demonstrates anti-OSCC properties but is hindered by poor solubility and bioavailability.
- Existing treatments necessitate improved drug delivery systems and diagnostic tools for OSCC management.
Purpose of the Study:
- To develop a multifunctional nanoparticle system for enhanced OSCC therapy and pathological ion detection.
- To overcome the limitations of resveratrol (RV) by improving its solubility and bioavailability for OSCC treatment.
- To create a fluorescence-responsive platform for detecting OSCC-related ions and mediating ferroptosis-associated therapy.
Main Methods:
- Fabrication of a polymer hybrid nanoparticle (poly(lactic-co-glycolic acid)-PLGA) modified with specific compounds (compound 1, 4-(trimethoxysilyl)butanoic acid-TMSBA) and co-loaded with compound 2 and resveratrol (RV).
- Evaluation of the nanoparticle's fluorescence selectivity and sensitivity towards OSCC-related glutathione (GSH⁻) and iron (Fe³⁺) ions.
- Assessment of resveratrol-loaded nanoparticle (RV-NPs) efficacy on CAL-27 cell proliferation using CCK-8 assays and investigation of the antitumor mechanism via qRT-PCR analysis of ferroptosis regulators.
Main Results:
- The developed nanoparticles (1-PLGA-TMSBA@2@RV) showed high fluorescence selectivity for GSH⁻ (98% quenching) and Fe³⁺ (92.9% quenching), with a wide detection range for GSH⁻ (10⁻⁷-10⁻² M) and a low detection limit for Fe³⁺ (10⁻⁶ M).
- RV-NPs significantly inhibited CAL-27 cell proliferation (53.8% higher efficacy than free RV), while blank carriers exhibited good biocompatibility.
- qRT-PCR analysis indicated that RV-NPs downregulated the ferroptosis regulator SLC7A11 by 71.2%, suggesting a ferroptosis-mediated antitumor effect.
Conclusions:
- The developed nanoplatform effectively integrates enhanced OSCC therapy with real-time pathological ion detection.
- The nanoparticle system overcomes resveratrol's limitations, offering improved bioavailability and targeted delivery for OSCC treatment.
- The findings suggest a promising ferroptosis-associated therapeutic strategy for OSCC, coupled with advanced diagnostic capabilities.
