A versatile supramolecular nanoagent for three-pronged boosting chemodynamic therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Chemodynamic therapy (CDT) shows promise for cancer treatment but is limited by tumor microenvironment factors like low acidity, insufficient hydrogen peroxide (H2O2), and high reduced glutathione (GSH) levels.
• Existing CDT materials struggle to overcome these limitations simultaneously, particularly supramolecular agents lacking intrinsic Fenton reaction capabilities.

Purpose of the Study:

• To develop a versatile supramolecular nanoagent (GOx@GANPs) that overcomes CDT limitations and enhances antitumor efficacy.
• To investigate the synergistic effects of CDT with starvation therapy and chemotherapy using the developed nanoagent.

Main Methods:

• Fabrication of GOx@GANPs using host-guest interactions between pillar[6]arene and ferrocene.
• Utilizing glucose oxidase (GOx) for in situ conversion of glucose to H+ and H2O2, optimizing Fenton reaction conditions.
• Employing a GSH-responsive gambogic acid prodrug and inhibiting ATP supply to deplete intracellular GSH and prevent its regeneration.

Main Results:

• GOx@GANPs successfully generated sufficient hydroxyl radicals (•OH) by optimizing intracellular conditions and depleting GSH.
• The nanoagent demonstrated effective suppression of •OH scavenging due to complete GSH exhaustion.
• Synergistic antitumor effects were observed through combined starvation therapy, chemotherapy, and CDT, with low toxicity to normal tissues.

Conclusions:

• The developed GOx@GANPs nanoagent effectively enhances CDT efficacy by addressing key limitations within the tumor microenvironment.
• This supramolecular approach offers a promising strategy for optimizing CDT and achieving synergistic tumor treatment.