ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(10):1773-1780. doi:10.7150/jca.84066 This issue Cite
Research Paper
Enhanced Therapeutic Effects of an Antitumor Agent on Subcutaneous Tumors in Mice by Photomechanical Wave-based Transvascular Drug Delivery
1. Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, Japan.
2. Department of Basic Pathology, National Defense Medical College, Japan.
3. Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Japan.
Abstract
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/cm2). 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.
Keywords: photomechanical wave, laser-induced stress wave, transvascular drug delivery, drug delivery system, cisplatin, chemotherapy
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