マサムネ ケン   MASAMUNE Ken
  正宗 賢
   所属   研究施設 研究施設
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Function of Epirubicin-Conjugated Polymeric Micelles in Sonodynamic Therapy
掲載誌名 正式名:Frontiers in Pharmacology
略  称:Front Pharmacol.
ISSNコード:16639812
掲載区分国外
巻・号・頁 10,546頁
著者・共著者 TAKEMAE Kazuhisa† , OKAMOTO Jun, HORISE Yuki, MASAMUNE Ken, MURAGAKI Yoshihiro
発行年月 2019/05/21
概要 The combinatory use of high-intensity focused ultrasound (HIFU) and epirubicin (EPI)-conjugated polymeric micellar nanoparticles (NC-6300) is thought to be a less invasive and more efficient method of cancer therapy. To investigate the mechanism underlying the combination effect, we examined the effect of trigger-pulsed HIFU (TP-HIFU) and NC-6300 from the perspective of reactive oxygen species (ROS) generation, which is considered the primary function of sonodynamic therapy (SDT), and changes in drug characteristics. TP-HIFU is an effective sequence for generating hydroxyl radicals to kill cancer cells. EPI was susceptible to degradation by TP-HIFU through the production of hydroxyl radicals. In contrast, EPI degradation of NC-6300 was suppressed by the hydrophilic shell of the micelles. NC-6300 also exhibited a sonosensitizer function, which promoted the generation of superoxide anions by TP-HIFU irradiation. The amount of ROS produced by TP-HIFU reached a level that caused structural changes to the cellular membrane. In conclusion, drug-conjugated micellar nanoparticles are more desirable for SDT because of accelerated ROS production and drug protection from ROS. Furthermore, a combination of NC-6300 and TP-HIFU is useful for minimally invasive cancer therapy with cooperative effects of HIFU-derived features, antitumor activity of EPI, and increased ROS generation to cause damage to cancer cells.
DOI 10.3389/fphar.2019.00546
PMID 31164824