Singzyme: A Single-Molecule Enzyme-Like Photocatalyst Powered by the Super Cage Effect

Area of Science:

• Supramolecular chemistry
• Photocatalysis
• Cancer therapy

Background:

• Photodynamic therapy (PDT) efficacy is limited by photosensitivity and reactive oxygen species (ROS) generation.
• Engineered photosensitizers are needed for enhanced light absorption, catalytic performance, and tumor microenvironment adaptation.

Purpose of the Study:

• To develop a single-molecule enzyme-like photocatalyst (superphane 1) for enhanced photodynamic therapy.
• To investigate its properties including photosensitivity, ROS generation, and multi-enzyme mimetic activities.

Main Methods:

• Design and synthesis of a superphane-based singzyme (1) with densely arranged phenothiazine units.
• Evaluation of singlet oxygen (1O2) yield under 450 nm irradiation.
• Assessment of catalytic efficiency for NADH and GSH oxidation, mimicking NADH oxidase and GSH oxidase.

Main Results:

• Superphane 1 achieved a 70% singlet oxygen yield, outperforming control compounds.
• Singzyme 1 demonstrated efficient catalytic activity towards NADH and GSH, inducing an intracellular 'oxygen burst' effect.
• The compound selectively depleted NADH and GSH, inhibiting mitochondrial oxidative phosphorylation and promoting apoptosis and ferroptosis.

Conclusions:

• Superphane-based singzyme 1 offers enhanced photosensitivity and superior ROS generation for PDT.
• Its multi-enzyme mimetic activity and biocompatibility provide a versatile platform for precision cancer therapy.
• This work advances single-molecule enzyme mimicry for therapeutic applications.