Defective Engineered Metal-Organic Frameworks for Tumor Cell-Specific Combined Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Cancer theranostics require innovative combination therapies for improved efficacy.
• Metal-organic frameworks (MOFs) offer versatile platforms for drug delivery and therapy.
• Targeted delivery systems are crucial for enhancing therapeutic outcomes and reducing side effects.

Purpose of the Study:

• To develop a hyaluronic-acid-functionalized defective metal-organic framework (Fe-UiO@HA) as an integrated nanoplatform.
• To combine phototherapy and chemodynamic therapy for synergistic cancer treatment.
• To enhance tumor-specific accumulation and therapeutic efficacy via CD44 receptor targeting.

Main Methods:

• Synthesis and characterization of Fe-UiO@HA nanoplatform.
• Evaluation of glutathione oxidase (GSHOx) and Fenton-like catalytic activities.
• Assessment of photocatalytic activity for reactive oxygen species (ROS) generation.
• Investigation of CD44-mediated cellular uptake and targeting efficiency.
• In vitro and in vivo evaluation of synergistic therapeutic effects.

Main Results:

• Fe-UiO@HA demonstrated effective depletion of intracellular glutathione (GSH) and decomposition of hydrogen peroxide (H2O2).
• The nanoplatform exhibited enhanced photocatalytic activity, leading to increased ROS generation in cancer cells.
• Hyaluronic acid (HA) functionalization promoted targeted accumulation and uptake by CD44-overexpressing tumor cells.
• The combined phototherapy and chemodynamic therapy approach showed significant synergistic anticancer effects.

Conclusions:

• The developed Fe-UiO@HA nanoplatform serves as an effective "all-in-one" theranostic agent.
• Integration of phototherapy and chemodynamic therapy via this nanoplatform significantly enhances cancer treatment efficacy.
• Targeted delivery mediated by HA functionalization improves the therapeutic potential of the nanoplatform.