Activatable Photodynamic Therapy with Therapeutic Effect Prediction Based on a Self-correction Upconversion Nanoprobe

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Photodynamic therapy (PDT) shows promise for cancer treatment but faces challenges in selective cancer cell destruction and predicting therapeutic outcomes.
• Developing activatable phototoxicity and simultaneous therapeutic effect prediction is crucial for effective and safe PDT.

Purpose of the Study:

• To design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction.
• To achieve selective cancer cell destruction with minimized off-target damage.

Main Methods:

• Fabrication of a multishelled upconversion nanoprobe (UCNPs) modified with an antenna molecule, photosensitizer (Rose Bengal), a fluorescent dye (Cy3), and a quencher (QSY7) attached to a CaB substrate peptide.
• Utilizing Förster resonance energy transfer (FRET) for energy transfer from UCNPs to Cy3/Rose Bengal, quenched by QSY7.
• CaB-specific cleavage of the peptide releases QSY7, activating PDT and enabling CaB imaging via Cy3 fluorescence recovery.
• Employing UCNPs emission as an internal standard for self-corrected Cy3 fluorescence ratio (FI583/FI540) for therapeutic effect prediction.

Main Results:

• The nanoprobe demonstrated cathepsin B (CaB)-responsive activation of photodynamic therapy (PDT) upon intracellular cleavage of the peptide substrate.
• Successful generation of reactive oxygen species (ROS) for cancer cell destruction.
• Achieved in situ self-corrected prediction of therapeutic effects by measuring the fluorescence intensity ratio of Cy3 over UCNPs.
• Minimized off-target damage due to targeted activation.

Conclusions:

• The developed self-corrected upconversion nanoprobe offers a promising strategy for precise tumor therapy.
• This approach integrates activatable PDT with reliable therapeutic effect prediction.
• Significant potential for improving the efficacy and safety of cancer treatments.