Yu Xiao, Liu Jinyuan, Bauer Aaron, Wei Xianqing, Smith Steve, Ning Shipeng, Wang Congzhou
Nanoscience and Biomedical Engineering, South Dakota School of Mines and Technology, 501 E St Joseph Street, Rapid City, South Dakota 57701, USA.
Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
J Colloid Interface Sci. 2024 Dec 15;676:101-109. doi: 10.1016/j.jcis.2024.07.047. Epub 2024 Jul 14.
The Enhanced Permeability and Retention (EPR) effect, an elevated accumulation of drugs and nanoparticles in tumors versus in normal tissues, is a widely used concept in the field of cancer therapy. It assumes that the vasculature of solid tumors would possess abnormal, leaky endothelial cell barriers, allowing easy access of intravenous-delivered drugs and nanoparticles to tumor regions. However, the EPR effect is not always effective owing to the heterogeneity of tumor endothelium over time, location, and species. Herein, we introduce a unique nanoparticle-based approach, using MUC18-targeted gold nanorods coupled with mild hyperthermia, to specifically enhance tumor endothelial permeability. This improves the efficacy of traditional cancer therapy including photothermal therapy and anticancer drug delivery by increasing the transport of photo-absorbers and drugs across the tumor endothelium. Using single cell imaging tools and classic analytical approaches in molecular biology, we demonstrate that MUC18-targeted gold nanorods and mild hyperthermia enlarge the intercellular gaps of tumor endothelium by inducing circumferential actin remodeling, stress fiber formation, and cell contraction of adjacent endothelial cells. Considering MUC18 is overexpressed on a variety of tumor endothelium and cancer cells, this approach paves a new avenue to improve the efficacy of cancer therapy by actively enhancing the tumor endothelial permeability.
增强渗透与滞留（EPR）效应是指药物和纳米颗粒在肿瘤组织中的蓄积量高于正常组织，这是癌症治疗领域广泛应用的一个概念。该效应假定实体瘤的脉管系统具有异常的、有渗漏的内皮细胞屏障，使得静脉注射的药物和纳米颗粒能够轻易进入肿瘤区域。然而，由于肿瘤内皮在时间、位置和物种上的异质性，EPR效应并不总是有效。在此，我们介绍一种独特的基于纳米颗粒的方法，即使用靶向MUC18的金纳米棒并结合温和热疗，以特异性增强肿瘤内皮的通透性。这通过增加光吸收剂和药物跨肿瘤内皮的转运，提高了包括光热疗法和抗癌药物递送在内的传统癌症治疗的疗效。利用单细胞成像工具和分子生物学中的经典分析方法，我们证明靶向MUC18的金纳米棒和温和热疗通过诱导周向肌动蛋白重塑、应力纤维形成以及相邻内皮细胞的细胞收缩，扩大了肿瘤内皮的细胞间隙。鉴于MUC18在多种肿瘤内皮和癌细胞上过度表达，这种方法为通过积极增强肿瘤内皮通透性来提高癌症治疗疗效开辟了一条新途径。
