Targeting-triggered porphysome nanostructure disruption for activatable photodynamic therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Photomedicine

Background:

• Photodynamic therapy (PDT) and photothermal therapy (PTT) offer targeted treatment options.
• PDT uses singlet oxygen for cell death, preserving tissue, unlike PTT's thermal necrosis.
• Activatable photosensitizers enhance treatment selectivity through disease-specific mechanisms.

Purpose of the Study:

• To develop folate-conjugated porphysomes as targeting-triggered activatable nano-beacons for PDT.
• To investigate the mechanism of porphysome nanostructure disruption and subsequent PDT activation.
• To evaluate the selective tumor ablation efficacy of folate-porphysomes in vitro and in vivo.

Main Methods:

• Synthesis and characterization of folate-conjugated porphysomes.
• Investigation of folate-receptor-mediated endocytosis and nanostructure disruption.
• In vitro and in vivo studies assessing PDT efficacy and tumor selectivity.

Main Results:

• Folate-porphysomes were efficiently internalized into folate-receptor-expressing cells.
• Internalization led to nanostructure disruption, reactivating porphyrin's photodynamic activity.
• Targeting-triggered PDT activation resulted in selective tumor ablation in both in vitro and in vivo models.

Conclusions:

• Folate-porphysomes serve as robust, targeting-triggered activatable photosensitizers for selective PDT.
• This approach enables highly specific tumor ablation while preserving surrounding tissue.
• Porphysome formulations can be adapted with various targeting ligands for personalized cancer therapy.