Photodynamic therapy using hemagglutinating virus of Japan envelope (HVJ-E): a novel therapeutic approach for the treatment of hormone antagonistic prostate cancer

摘要

Traditional treatment options for prostate cancer are insufficient to cure advanced drug-resistant prostate cancer. Thus, as an alternative form of cancer therapy, photodynamic therapy (PDT) has become the main subject of intense investigation as a possible treatment modality, In this study, ultraviolet-inactivated viral vector, called hemagglutinating virus of Japan envelope (HVJ-E) was utilized to establish an effective delivery system for photosensitizer. Lipidated protoporphyrin Ⅸ (PpⅨ lipid) was inserted in HVJ-E by centrifugation to create a new drug delivering system that allows selective accumulation of photosensitizers in cancer cells. To study in vitro drug release mechanism of porphyrus envelope, the ultra-high voltage electron microscope tomography was applied. Next, to evaluate the photodynamic efficiency of porphyrus envelope for hormone antagonistic prostate cancer cells (PC-3), uptake of porphyrus envelope derived PpⅨ lipid and PpⅨ induced from exogenously administered precursor of 5-aminolevulinic acid hydrochloride (5-ALA) were compared by measuring fluorescence intensity of PpⅨ. Finally, to evaluate the efficacy of porphyrus envelope-PDT, laser light at a wavelength of 405 nm was irradiated to PC-3 cells. As a result, incorporation of porphyrus envelope-derived PpⅨ lipid occurred via membrane fusion, giving the highest fluorescence intensity when compared to 5-ALA-induced PpⅨ. Also, results from PDT experiment revealed the 28.6 × 10~3-fold and 206-fold increase in therapeutic efficacy when compared to those of PDT using 5-ALA induced PpⅨ and PpⅨ lipid, respectively. Our findings suggest how porphyrus envelope can induce efficient accumulation of PpⅨ lipid, which can enhance the therapeutic efficacy of PDT against hormone antagonistic prostate cancer.