Heavy-Atom-Free Photosensitizer-Loaded Lipid Nanocapsules for Photodynamic Therapy.

Area of Science:

• Nanomedicine
• Photochemistry
• Cancer Therapy

Background:

• Photodynamic therapy (PDT) utilizes photosensitizers (PS) to generate reactive oxygen species (ROS) for cancer treatment.
• Hydrophobicity of PS hinders effective delivery in PDT.
• Heavy-atom-free PS (HAF-PS) offer a promising alternative for PDT improvement.

Purpose of the Study:

• To develop and evaluate HAF-PS encapsulated in lipid nanocapsules (LNCs) for enhanced PDT.
• To investigate the singlet oxygen generation and photocytotoxicity of these novel formulations.
• To demonstrate the potential of LNCs as a drug delivery system for HAF-PS.

Main Methods:

• Encapsulation of perylenediimide (PDI) based HAF-PS (O-PDI and 1S-PDI) into LNCs using a solvent-free phase-inversion temperature (PIT) method.
• Quantification of singlet oxygen quantum yield (φSOQY) using 1,3-diphenylisobenzofuran (DPBF) as a trap.
• In vitro cytotoxicity and photocytotoxicity studies on cancer cells.
• Cellular internalization studies using fluorescently labeled PDI-loaded LNCs (O-PDI@LNC) in U-87 MG cells.

Main Results:

• HAF-PS-loaded LNCs (1S-PDI@LNC) efficiently generated singlet oxygen (¹O₂) in a biorelevant environment (φSOQY = 0.52).
• 1S-PDI demonstrated a high singlet oxygen quantum yield (φSOQY = 0.94).
• 1S-PDI@LNC exhibited low dark toxicity but significantly enhanced photocytotoxicity upon illumination.
• Cellular uptake of O-PDI@LNC was confirmed in U-87 MG cells.

Conclusions:

• Lipid nanocapsules are an effective carrier for hydrophobic HAF-PS, improving their performance in PDT.
• The developed 1S-PDI@LNC formulation shows significant potential for minimally invasive cancer therapy.
• This strategy advances the development of novel HAF-PS delivery systems for improved phototherapeutic outcomes.