A biodegradable covalent organic framework for synergistic tumor therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Stimulus-responsive nanocarriers are crucial for targeted cancer drug delivery.
• Developing biodegradable nanocarriers that selectively target tumors remains a challenge.

Purpose of the Study:

• To develop a novel redox-responsive, biodegradable, porphyrin-based covalent organic framework (COF) for targeted cancer therapy.
• To investigate the synergistic effects of chemotherapy and photodynamic therapy (PDT) mediated by the COF in a tumor microenvironment.

Main Methods:

• Synthesized a disulfide-linked porphyrin COF.
• Loaded the COF with 5-fluorouracil (5-Fu) to create a nano-drug delivery system.
• Investigated GSH-triggered biodegradation and drug release.
• Evaluated combined chemotherapy and PDT efficacy in MCF-7 breast cancer models, focusing on ferroptosis induction.

Main Results:

• The COF demonstrated glutathione (GSH)-triggered nanocrystallization and biodegradation.
• Efficient release of 5-Fu from the COF within tumor cells was achieved.
• Synergistic anti-tumor effects were observed through enhanced chemotherapy and GSH depletion-boosted PDT.
• Therapeutic efficacy was improved with reduced side effects due to targeting tumor-specific high GSH concentrations.

Conclusions:

• The developed GSH-responsive COF nanoagent enables targeted drug delivery and synergistic chemo-photodynamic therapy.
• This approach effectively utilizes the tumor microenvironment's abnormalities for enhanced cancer treatment.
• The study presents a promising strategy for improving anti-cancer therapy by combining targeted drug release and enhanced PDT.