Enhanced Therapeutic Effects of an Antitumor Agent on Subcutaneous Tumors in Mice by Photomechanical Wave-based Transvascular Drug Delivery

Purpose: We previously developed a site-selective transvascular drug delivery system based on nanosecond pulsed laser-induced photomechanical waves (PMWs). In this study, we applied this method to the delivery of cisplatin (cis-diamminedichloroplatinum, CDDP) to a subcutaneous tumor in a mouse and examined its antitumor effects. Methods: A mouse tumor model with subcutaneous inoculation of human head and neck cancer cells (FaDu cells) was used. The mice were divided into four groups: control without any treatment (control), CDDP application only (CDDP only), PMW application only (PMW only) and combined application of PMWs and CDDP (PMW+CDDP). A PMW was generated by irradiating a laser target, which was placed on the skin over the tumor, with a ruby laser pulse (fluence, 1.6 J/cm(2)). A CDDP solution was intraperitoneally injected into the mice (2.5 mg/kg). Results: Until 7 days posttreatment, the tumor volume in the control group monotonically increased, while the tumor volumes in the CDDP-only group and PMW-only group did not change greatly and that in the PMW+CDDP group slightly decreased. Afterward, the tumors started to regrow in all treatment groups, but the tumor growth rate was considerably low in the PMW+CDDP group. There was a significant difference in the time courses of tumor volume between the PMW+CDDP group and the control group for up to 14 days posttreatment. The ratio of the Ki-67-positive (proliferative) areas to the whole tumor regions in the PMW+CDDP group was significantly smaller than that in the control group at 7 days posttreatment. These results are attributable to the synergistic effects of enhanced extravasation of CDDP and mechanical tumoricidal effect by PMWs. Conclusion: The combined application of CDDP and PMWs significantly improved the antitumor effects on mouse subcutaneous tumors.