FeP-Based Nanotheranostic Platform for Enhanced Phototherapy/Ferroptosis/Chemodynamic Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Ferroptosis is an iron-dependent cell death pathway crucial for cancer therapy, but its efficacy is limited by insufficient iron and reactive oxygen species (ROS).
• Existing ferroptosis inducers often face challenges with endogenous iron and ROS levels, hindering their therapeutic potential.
• Developing novel strategies to enhance ferroptosis and overcome these limitations is critical for advancing cancer treatment.

Purpose of the Study:

• To develop a near-infrared (NIR) photo-responsive iron porphyrin-based nanoparticle (FeP@PEG NPs) to enhance ferroptosis and cancer therapy.
• To investigate the synergistic effects of photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) mediated by FeP@PEG NPs.
• To evaluate the theranostic potential of FeP@PEG NPs, including their anticancer efficacy and magnetic resonance imaging (MRI) properties.

Main Methods:

• Fabrication of NIR photo-responsive FeP@PEG NPs.
• Investigation of FeP@PEG NPs' ability to deplete glutathione (GSH) and inactivate glutathione peroxide 4 (GPX4).
• Assessment of ·OH generation via Fenton reaction and lipid peroxide accumulation.
• Evaluation of cell apoptosis induction via mitochondrial dysfunction under NIR irradiation.
• In vitro and in vivo studies on cancer cell growth inhibition.
• T2-weighted MRI property assessment.

Main Results:

• FeP@PEG NPs effectively enhanced ferroptosis by increasing exogenous iron, depleting GSH, and inactivating GPX4.
• NIR irradiation of FeP@PEG NPs induced PTT and PDT, leading to enhanced cancer cell apoptosis and lipid peroxide accumulation.
• FeP@PEG NPs demonstrated significant inhibition of cancer cell growth in vitro and in vivo.
• The nanoparticles exhibited excellent T2-weighted MRI properties for potential diagnostic applications.
• Synergistic effects of PTT, PDT, and CDT were observed, leading to enhanced therapeutic outcomes.

Conclusions:

• FeP@PEG NPs serve as an effective platform for enhancing ferroptosis and cancer therapy.
• The developed nanotheranostic platform integrates enhanced phototherapy, ferroptosis, and chemodynamic therapy for improved cancer treatment.
• FeP@PEG NPs show promise for clinical cancer theranostics due to their combined therapeutic and imaging capabilities.