Hybrid protein-peptide system for the selective pH-dependent binding and photodynamic ablation of cancer cells

Area of Science:

• Biomedical Engineering
• Molecular Oncology
• Photochemistry

Background:

• Photodynamic therapy (PDT) is a promising cancer treatment but lacks specificity, causing side effects.
• Developing targeted PDT agents is crucial to enhance efficacy and reduce damage to healthy tissues.
• Cancer cells exhibit a lower extracellular pH, a characteristic exploitable for targeted drug delivery.

Purpose of the Study:

• To engineer a hybrid protein-peptide photosensitizer for selective cancer cell targeting and ablation.
• To leverage the pH-dependent binding of the pHLIP peptide for targeted delivery of a photosensitizer.
• To evaluate the efficacy of the developed system in killing cancer cells under specific pH conditions and light exposure.

Main Methods:

• Constructed a fusion protein combining the miniSOG photosensitizer with the pH-Low Insertion Peptide (pHLIP).
• Utilized HeLa cancer cells to assess the pH-dependent binding and phototoxicity of the protein-peptide system.
• Investigated the selective binding of the construct at extracellular pH below 6.8 and subsequent cell killing upon light activation.

Main Results:

• The hybrid protein-peptide system demonstrated selective binding to HeLa cells in an acidic extracellular environment (pH < 6.8).
• Light exposure of the bound system resulted in effective photodynamic ablation of cancer cells.
• The study confirmed the feasibility of using genetically encoded MiniSOG-pHLIP fusions for targeted PDT.

Conclusions:

• Genetically engineered MiniSOG-pHLIP fusions offer a novel strategy for targeted cancer therapy.
• This approach enables precise photodynamic cancer cell destruction by exploiting the acidic tumor microenvironment.
• The developed system holds potential for improving the safety and efficacy of photodynamic therapy.