Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone-Pyridine Tautomer...

Area of Science:

• Biomedical Engineering
• Materials Science
• Photodynamic Therapy

Background:

• Photodynamic therapy (PDT) efficacy is limited by tumor hypoxia and poor light penetration.
• Conventional singlet oxygen batteries (SOBs) suffer from uncontrolled "always-ON" singlet oxygen release, causing leakage and safety concerns.
• Existing SOBs lack spatiotemporal control over singlet oxygen generation.

Purpose of the Study:

• To develop a programmable singlet oxygen battery (SOB) with controlled "OFF-ON-OFF" singlet oxygen release.
• To engineer a tumor-microenvironment-responsive switch for selective singlet oxygen delivery.
• To enhance PDT efficacy and biosafety by addressing limitations of current SOB systems.

Main Methods:

• Development of a pyridone-pyridine switch (PyAce) with distinct singlet oxygen storage half-lives.
• Utilizing PyAce's tautomeric forms (PyAce-0 and PyAce) for controlled singlet oxygen release.
• Demonstrating tumor-microenvironment-triggered switching for targeted singlet oxygen generation.

Main Results:

• PyAce exhibits a long singlet oxygen storage half-life (18.5 h) in its native pyridone form.
• Tumor microenvironment triggers PyAce conversion to pyridine form, enabling rapid singlet oxygen release (16 min half-life).
• Achieved "OFF-ON-OFF" singlet oxygen therapy with high spatiotemporal selectivity, independent of oxygen and light.

Conclusions:

• The programmable PyAce-based SOB system effectively controls singlet oxygen release.
• This approach overcomes limitations of hypoxia and light penetration in PDT.
• The developed system offers enhanced therapeutic efficacy and improved biosafety for cancer treatment.