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用于脑肿瘤血管靶向间质光动力治疗的多功能超小型纳米平台,由实时磁共振成像引导

Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI.

作者信息

Bechet Denise, Auger Florent, Couleaud Pierre, Marty Eric, Ravasi Laura, Durieux Nicolas, Bonnet Corinne, Plénat François, Frochot Céline, Mordon Serge, Tillement Olivier, Vanderesse Régis, Lux François, Perriat Pascal, Guillemin François, Barberi-Heyob Muriel

机构信息

CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.

IMPRT (Institut de Médecine Prédictive et de Recherche Thérapeutique) IFR 114, U 837 INSERM, CHRU de Lille, Lille, France.

出版信息

Nanomedicine. 2015 Apr;11(3):657-70. doi: 10.1016/j.nano.2014.12.007. Epub 2015 Jan 31.

Abstract

Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. A number of studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. From the clinical editor: The authors constructed tumor vascular peptide targeting multifunctional silica-based nanoparticles, with encapsulated gadolinium oxide as MRI contrast agent and chlorin as a photosensitizer, as a proof of concept novel treatment for glioblastoma in an animal model.

摘要

脑肿瘤的光动力疗法(PDT)似乎是传统治疗方法的补充。多项研究表明,血管效应在PDT根除肿瘤中起主要作用。对于由实时成像引导的脑肿瘤间质光动力疗法(iPDT),已经设计了由表面定位的肿瘤血管靶向神经纤毛蛋白-1(NRP-1)肽、封装的光敏剂和磁共振成像(MRI)造影剂组成的多功能纳米颗粒。纳米平台赋予细胞光敏性,并显示出对NRP-1的分子亲和力。向患有颅内胶质瘤的大鼠静脉注射后,对主要位于肿瘤周边的新生血管内衬的血管生成内皮细胞进行了动态对比增强MRI检查。通过利用肿瘤及肿瘤相邻脑组织的NRP-1蛋白表达完成的MRI,我们检查了纳米颗粒的选择性。本研究代表了使用靶向超小纳米平台通过实时MRI引导进行闭颅脑内iPDT的首个体内概念验证。临床编辑评论:作者构建了肿瘤血管肽靶向多功能二氧化硅基纳米颗粒,其中封装氧化钆作为MRI造影剂,二氢卟吩作为光敏剂,作为动物模型中胶质母细胞瘤新型治疗方法的概念验证。

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