Tahara Yu, Yoshikawa Takuma, Sato Hikari, Mori Yukina, Zahangir Md Hosain, Kishimura Akihiro, Mori Takeshi, Katayama Yoshiki
Graduate School of Systems Life Sciences , Kyushu University , 744 Motooka , Nishi-ku , Fukuoka 819-0395 , Japan . Email:
Department of Applied Chemistry , Faculty of Engineering , Kyushu University , 744 Motooka , Nishi-ku , Fukuoka 819-0395 , Japan.
Medchemcomm. 2016 Dec 21;8(2):415-421. doi: 10.1039/c6md00614k. eCollection 2017 Feb 1.
We propose a method to improve the enhanced permeability and retention (EPR) effect of nanomedicines based on tumor-specific vasodilation using a nitric oxide (NO) donor-containing liposome. NONOate, a typical NO donor, was incorporated into a PEGylated liposome to retard the protonation-induced release of NO from NONOate by the protecting lipid bilayer membrane. The NONOate-containing liposome (NONOate-LP) showed similar blood retention to an empty PEGylated liposome but almost twice the amount accumulated within the tumor. This improvement in the EPR effect is thought to have been caused by specific vasodilation in the tumor tissue by NO released from the NONOate-LP accumulated in the tumor. The improved EPR effect by NONOate-LP will be useful for the accumulation of co-administered nanomedicines.
我们提出了一种基于肿瘤特异性血管舒张来改善纳米药物的增强渗透与滞留（EPR）效应的方法，该方法使用了含一氧化氮（NO）供体的脂质体。典型的NO供体NONOate被整合到聚乙二醇化脂质体中，以通过保护性脂质双层膜延缓质子化诱导的NONOate释放NO。含NONOate的脂质体（NONOate-LP）与空的聚乙二醇化脂质体具有相似的血液滞留时间，但在肿瘤内积累的量几乎是其两倍。这种EPR效应的改善被认为是由积聚在肿瘤中的NONOate-LP释放的NO引起肿瘤组织中的特异性血管舒张所致。NONOate-LP改善的EPR效应将有助于共同给药的纳米药物的积累。
