Multifunctional Nanoparticles for Enhanced Chemodynamic/Photodynamic Therapy through a Photothermal, H₂O₂-Elevation,...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Chemodynamic therapy (CDT) and photodynamic therapy (PDT) show promise in cancer treatment.
• Combining CDT and PDT offers synergistic therapeutic effects.
• Enhancing the efficacy of combined CDT/PDT remains a significant challenge.

Purpose of the Study:

• To develop an integrated nanosystem for triply enhanced chemodynamic and photodynamic therapy.
• To investigate the synergistic effects of photothermal therapy, hydrogen peroxide elevation, and glutathione consumption.
• To create an active targeting nanoparticle for improved cellular internalization and therapeutic outcome.

Main Methods:

• Fabrication of nano-ZIF-8 vesicles encapsulating ferrocene derivatives (Fc-BE) and photosensitizers (IR825).
• Surface modification with cinnamaldehyde-hyaluronic acid (HA-CA) for CD44 receptor targeting.
• Evaluation of nanoparticle performance in cellular internalization, reactive oxygen species generation, and therapeutic efficacy.

Main Results:

• The developed nanoparticles (NPs@Fc-BE&IR825) effectively targeted CD44-expressing cells.
• HA-CA coating enhanced intracellular hydrogen peroxide levels.
• Fc-BE released in cells consumed glutathione and catalyzed hydrogen peroxide to generate hydroxyl radicals.
• NIR irradiation amplified hydroxyl radical and singlet oxygen production, leading to increased oxidative stress.

Conclusions:

• The integrated nanosystem demonstrates a triply enhanced CDT/PDT effect through photothermal action, H2O2 elevation, and GSH depletion.
• This approach significantly amplifies oxidative stress for potent cancer therapy.
• The developed nanoparticles represent a promising platform for highly effective combined chemodynamic and photodynamic cancer treatment.