5,10,15,20-Tetrakis(
benzo[b]thiophene)
porphyrin (BTP) is a newly synthesized hydrophobic
photosensitizer with fluorescence quantum yield in
toluene: ΦF=0.062. Previously, its limitations in solubility had hindered scientific experimentation regarding its photodynamic effects on
cancer cells. By utilizing various compositions of
liposomes in order to alter the solubility of BTP, the photocytotoxicity,
reactive oxygen species generation, and subcellular localization of the liposomal BTP were identified in this work. DNA fragmentation and high content screening assays were performed in order to shed light on the tumoricidal mechanism of the liposomal
photosensitizer. The MTT assay results showed promising results in the irradiation specific
PDT activity against MCF-7 cells in all liposomal compositions. Production of ROS was confirmed in the liposomal BTP treated MCF-7 cells after irradiation in a concentration dependent manner. The subcellular localization assays revealed that the localization of BTP was dependent on both the
photosensitizer's chemical properties and the properties of the delivery agent encapsulating aforesaid substance. Significant DNA fragmentation was observed in both nucleus localizing liposomal BTP, BTP encapsulated
DOPC and DOPE (
DOPC-BTP and DOPE-BTP), treated MCF-7 cells. All liposomal-BTPs were successful in inducing mitochondrial permeability transition, an increase in the permeability of the mitochondrial membrane, and activating
caspase-3/7. ER localizing BTP were able to significantly increase the cytosolic
calcium levels by
photodynamic therapy, confirming the photodynamic ability of ER localized BTP to damage the ER membrane. The application of
liposomes in delivering a novel hydrophobic
photosensitizer, BTP, and
photodynamic therapy treatment against MCF-7 cells were successful. It was confirmed that the MCF-7 cell death pathway via
photodynamic therapy was altered in a controlled manner by controlling the intracellular localization of the
photosensitizer through
lipid composition adjustment.