Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585, Singapore.
Department of Chemistry, Missouri University of Science & Technology , Rolla, Missouri 65409, United States.
ACS Nano. 2016 Jan 26;10(1):1170-81. doi: 10.1021/acsnano.5b06487. Epub 2015 Dec 10.
Cancer nanomedicine vehicles are required to cross the vascular barrier to reach the tumor site in order to ensure the successful delivery of their therapeutic load. Here, nanodiamond (ND) variants were shown to induce surface dependent vascular barrier leakiness. The ND-induced leakiness was found to be mediated by the increase in intracellular reactive oxygen species (ROS) and Ca(2+). These then in turn triggered the loss in endothelial cell-endothelial cell connections of the vascular barrier and also triggered their quasi-stable cytoskeletal remodelling. This ND driven increase in leakiness allowed more doxorubicin drug to penetrate through the vascular barrier to reach the cancer cells. This increase in the doxorubicin penetration subsequently led to an increase in the cancer killing effect. Overall, tuning the vascular barrier leakiness through ND surface group functionalization could provide an alternative strategy for the cancer nanomedicine to traverse across the vascular barrier.
癌症纳米医学载体需要穿过血管屏障到达肿瘤部位，以确保其治疗负荷的成功传递。在这里，纳米金刚石（ND）变体被证明可以诱导表面依赖性血管屏障通透性增加。ND 诱导的通透性增加是通过细胞内活性氧（ROS）和 Ca(2+)的增加来介导的。这些反过来又触发了血管屏障内皮细胞-内皮细胞连接的丧失，并触发了它们的准稳定细胞骨架重塑。这种由 ND 驱动的通透性增加使更多的多柔比星药物穿透血管屏障到达癌细胞。这种多柔比星渗透的增加随后导致癌细胞杀伤效果的增加。总的来说，通过 ND 表面基团功能化来调节血管屏障通透性，可以为癌症纳米医学穿过血管屏障提供一种替代策略。
