文章：

AGuIX®诊疗纳米颗粒靶向血管的临床前光动力疗法研究

Preclinical Photodynamic Therapy Targeting Blood Vessels with AGuIX®Theranostic Nanoparticles

原文发布日期：23 November 2024

DOI: 10.3390/cancers16233924

类型: Article

开放获取: 是

英文摘要：

Background:Glioblastoma multiforme (GBM) is the most common highly aggressive, primary malignant brain tumor in adults. Current experimental strategies include photodynamic therapy (PDT) and new drug delivery technologies such as nanoparticles, which could play a key role in the treatment, diagnosis, and imaging of brain tumors.Objectives:The purpose of this study was to test the efficacy of PDT using AGuIX-TPP, a polysiloxane-based nanoparticle (AGuIX) that contains TPP (5,10,15,20-tetraphenyl-21H,23H-porphine), in biological models of glioblastoma multiforme and to investigate the vascular mechanisms of action at multiple complexity levels.Methods:PDT effects were studied in monolayer and spheroid cell culture, as well as tumors in chicken chorioallantoic membranes (CAMs) and in mice were studied.Results: Treatment was effective in both endothelial ECRF and glioma U87 cells, as well as in the inhibition of growth of the glioma spheroids. PDT using AGuIX-TPP inhibited U87 tumors growing in CAM and destroyed their vascularization. The U87 tumors were also grown in nude mice. Their vascular network, as well as oxygen partial pressure, were assessed using ultrasound and EPR oximetry. The treatment damaged tumor vessels and slightly decreased oxygen levels.Conclusions: PDT with AGuIX-TPP was effective against glioma cells, spheroids, and tumors; however, in mice, its efficacy appeared to be strongly related to the presence of blood vessels in the tumor before the treatment.

摘要翻译： 

背景：多形性胶质母细胞瘤（GBM）是成人中最常见的高度侵袭性原发性恶性脑肿瘤。当前实验性治疗策略包括光动力疗法（PDT）以及纳米颗粒等新型药物递送技术，这些技术在脑肿瘤的治疗、诊断和成像中可能发挥关键作用。 目的：本研究旨在测试基于聚硅氧烷的纳米颗粒（AGuIX）负载TPP（5,10,15,20-四苯基-21H,23H-卟啉）形成的AGuIX-TPP在胶质母细胞瘤生物模型中的PDT疗效，并从多复杂度层面探究其血管作用机制。 方法：在单层细胞培养、球状体细胞培养、鸡胚绒毛尿囊膜（CAM）肿瘤模型及小鼠肿瘤模型中研究PDT效应。 结果：该疗法对内皮细胞ECRF和胶质瘤U87细胞均显示疗效，并能抑制胶质瘤球状体生长。使用AGuIX-TPP的PDT能抑制CAM中生长的U87肿瘤并破坏其血管系统。在裸鼠体内培养的U87肿瘤中，通过超声和电子顺磁共振测氧法评估其血管网络及氧分压，发现治疗能损伤肿瘤血管并轻微降低氧含量。 结论：AGuIX-TPP介导的PDT对胶质瘤细胞、球状体及肿瘤均具有疗效；然而在小鼠模型中，其疗效似乎与治疗前肿瘤内血管的存在密切相关。

原文链接：

Preclinical Photodynamic Therapy Targeting Blood Vessels with AGuIX®Theranostic Nanoparticles