Physiologically Stable, Epitope-Imprinted, and Double-Gated Metal-Organic Framework Drug Delivery System for...

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Nanoscale metal-organic frameworks (MOFs) show promise for drug delivery but lack stability in physiological conditions.
• Phosphate-rich environments degrade MOFs, limiting their clinical use.
• Active-targeted delivery systems are crucial for personalized cancer therapies.

Purpose of the Study:

• To create a physiologically stable, epitope-imprinted, double-gated MOF drug delivery system.
• To enable tumor-targeted combination therapy using photodynamic therapy (PDT) and two-drug chemotherapy.
• To enhance drug targeting and achieve logic-gated release for precise cancer treatment.

Main Methods:

• Functionalized PCN-224(ZrIV) MOFs with silanes and loaded drug I.
• Utilized DNA as a gatekeeper (nanogate I) and nanocarrier for drug II via intercalation.
• Assembled epitope-imprinted ZIF-8 films (nanogate II) for phosphate resistance and cancer cell recognition.

Main Results:

• The double-gated MOF system demonstrated excellent physiological stability.
• Achieved selective targeting of cancer cells through imprinted ZIF-8 films.
• Minimized premature drug leakage and enabled logic-gated release for enhanced chemotherapy efficacy.

Conclusions:

• The developed double-gated MOF drug system offers superior physiological stability and active targeting to cancer cells.
• Successfully achieved combination therapy of PDT and two-drug chemotherapy.
• Presents broad application prospects in cancer gene therapy and nucleic acid vaccine development.