Ni Nengyi, Wang Weiyi, Sun Yu, Sun Xiao, Leong David Tai
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.
School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
Biomaterials. 2022 Aug;287:121640. doi: 10.1016/j.biomaterials.2022.121640. Epub 2022 Jun 21.
All intravenous delivered nanomedicine needs to escape from the blood vessel to exert their therapeutic efficacy at their designated site of action. Failure to do so increases the possibility of detrimental side effects and negates their therapeutic intent. Many powerful anticancer nanomedicine strategies rely solely on the tumor derived enhanced permeability and retention (EPR) effect for the only mode of escaping from the tumor vasculature. However, not all tumors have the EPR effect nor can the EPR effect be induced or controlled for its location and timeliness. In recent years, there have been exciting developments along the lines of inducing endothelial leakiness at the tumor to decrease the dependence of EPR. Physical disruption of the endothelial-endothelial cell junctions with coordinated biological intrinsic pathways have been proposed that includes various modalities like ultrasound, radiotherapy, heat and even nanoparticles, appear to show good progress towards the goal of inducing endothelial leakiness. This review explains the intricate and complex biological background behind the endothelial cells with linkages on how updated reported nanomedicine strategies managed to induce endothelial leakiness. This review will also end off with fresh insights on where the future of inducible endothelial leakiness holds.
所有通过静脉给药的纳米药物都需要从血管中逃逸出来，才能在其指定的作用部位发挥治疗效果。否则，会增加产生有害副作用的可能性，并使其治疗意图无法实现。许多强大的抗癌纳米药物策略仅依赖肿瘤衍生的增强渗透与滞留（EPR）效应作为从肿瘤脉管系统逃逸的唯一方式。然而，并非所有肿瘤都具有EPR效应，也无法对EPR效应的位置和时效性进行诱导或控制。近年来，在诱导肿瘤部位内皮细胞渗漏以减少对EPR的依赖方面取得了令人兴奋的进展。有人提出通过协调生物内在途径对内皮细胞间连接进行物理破坏，其中包括超声、放疗、热疗甚至纳米颗粒等各种方式，在诱导内皮细胞渗漏的目标上似乎取得了良好进展。这篇综述解释了内皮细胞背后复杂的生物学背景，以及最新报道的纳米药物策略如何诱导内皮细胞渗漏。这篇综述还将对可诱导内皮细胞渗漏的未来发展方向提出新的见解。
