Core-Shell Structured Metal-Organic Frameworks for pH-Triggered Combination Photodynamic/Chemotherapy-Based Cancer...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Hypoxic tumors pose a challenge for photodynamic therapy (PDT).
• Hypoxia-activated prodrugs offer a potential solution, but controlled release remains difficult.
• Metal-organic frameworks (MOFs) can be engineered for targeted drug delivery.

Purpose of the Study:

• To develop a core-shell MOF for enhanced PDT efficacy in hypoxic tumors.
• To achieve on-demand release of hypoxia-activated prodrugs (AQ4N) using a MOF system.
• To improve tumor targeting and therapeutic efficiency for hypoxic tumors.

Main Methods:

• Fabrication of a core-shell MOF by assembling zeolitic imidazolate frameworks (ZIF-8) onto AQ4N-loaded porphyrinic MOF.
• Surface functionalization with folic acid-conjugated polyethylene glycol for targeting.
• Investigating acidic environment-triggered release of AQ4N and laser-induced reactive oxygen species generation for PDT.

Main Results:

• The developed MOF system demonstrated controlled release of AQ4N triggered by acidic environments.
• Porphyrinic MOFs generated reactive oxygen species upon laser exposure for PDT.
• PDT-induced exacerbation of hypoxia led to AQ4N bioreduction to AQ4, enhancing anticancer activity.

Conclusions:

• The core-shell MOF system effectively delivers hypoxia-activated prodrugs for enhanced PDT in hypoxic tumors.
• This approach offers a practical strategy to overcome limitations of PDT in hypoxic tumor microenvironments.
• The developed MOF nanocomposite shows significant potential for improving tumor-targeting and therapeutic outcomes.