Efficient photodynamic therapy against drug-resistant prostate cancer using replication-deficient virus particles and talaporfin sodium

To enhance the potency of photosensitizer, we developed a novel photosensitizer, Laserphyrin (R)-HVJ-E (L-HVJ-E), by incorporating talaporfin sodium (Laserphyrin (R), Meiji Seika Pharma) into hemagglutinating virus of Japan envelope (HVJ-E). In this study, we examined the optimal Laserphyrin (R) concentration for preparation of Laserphyrin (R)-HVJ-E which had photocytotoxicity and maintained direct cytotoxicity derived from HVJ-E. Then, potency of Laserphyrin (R)-HVJ-E and Laserphyrin (R) were compared in vitro using castration-resistant prostate cancer cell line (PC-3). A laser diode (L660P120, Thorlabs, USA) with a wavelength of 664 nm was used for light activation of Laserphyrin (R), which corresponds to an absorption peak of Laserphyrin (R) and provides a high therapeutic efficiency. The photocytotoxicity and direct cytotoxicity of Laserphyrin (R)-HVJ-E prepared using various Laserphyrin (R) concentrations were evaluated using PC-3 cell in vitro. We categorized the treatment groups as Group 1: 50 mu L of D-MEM treatment group, Group 2: HVJ-E treatment group, Group 3: Laserphyrin (R)-HVJ-E treatment group, and Group 4: Laserphyrin (R) treatment group. Group 3 was subjected to different concentrations of Laserphyrin (R)-HVJ-E suspension, and all groups were subjected to different incubation periods (24, 48 h), (30 min, 1 h, or 3 h,) respectively, without and after PDT. Laserphyrin (R)-HVJ-E prepared using 15 mM Laserphyrin (R) had high photocytotoxicity and maintained HVJ-E's ability to induce direct cytotoxicity. Therapeutic effect of Laserphyrin (R)-HVJ-E was substantially equivalent to that of Laserphyrin (R) alone even at half Laserphyrin (R) concentration. By utilizing Laserphyrin (R)-HVJ-E, PDT could be performed with lower Laserphyrin (R) concentration. In addition, Laserphyrin (R)-HVJ-E showed higher potency than Laserphyrin (R) by combining cytotoxicities of HVJ-E and PDT.

Automated summary

The study found that Laserphyrin (R)-HVJ-E prepared with 15 mM of Laserphyrin (R) had high photocytotoxicity and maintained the ability of HVJ-E to induce direct cytotoxicity. The therapeutic effect of Laserphyrin (R)-HVJ-E was substantially equivalent to that of Laserphyrin (R) alone, even at half the concentration. By combining the cytotoxicities of HVJ-E and PDT, Laserphyrin (R)-HVJ-E showed higher potency than Laserphyrin (R).