In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative tumor delineation.
In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative tumor delineation.
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DOI：
10.1227/01.neu.0000344150.81021.aa
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发表时间：
2009-05
期刊：
影响因子：
4.8
通讯作者：
Sagher O
中科院分区：
文献类型：
--
作者：
Orringer DA;Koo YE;Chen T;Kim G;Hah HJ;Xu H;Wang S;Keep R;Philbert MA;Kopelman R;Sagher O
合成并完成一种新型肿瘤靶向纳米器械的体外表征，用于脑肿瘤的术中可见勾画。评价了含有亚甲蓝、考马斯亮蓝或吲哚菁绿色的染料负载的聚丙烯酰胺纳米颗粒（NP）在9L胶质瘤细胞系中引起颜色变化的能力。将细胞与负载染料的NP一起孵育，拍照，并进行比色分析。使用共聚焦显微镜来确定NP在处理的细胞中的亚细胞定位。神经胶质瘤细胞系与负载染料的NP的孵育导致以剂量和时间依赖性方式的清晰可见的、可定量的细胞标记。观察到负载染料的NP与表面结合并被神经胶质瘤细胞内化。用F3（一种与肿瘤细胞表面受体核仁素结合的肽）包被NP表面，显著增加了NP对神经胶质瘤细胞的亲和力。F3靶向也显著增加了负载染料的NP的细胞标记率。最后，F3靶向的纳米颗粒表现出特异性靶向各种癌细胞系的基础上，其表面表达的细胞表面核仁素。F3靶向染料负载的NP有效地引起神经胶质瘤细胞中的明确颜色变化。这份报告代表了靶向纳米颗粒的首次使用，以引起肿瘤细胞系的可见颜色变化。类似的纳米器件将来可能会用于在肿瘤切除过程中实现可见的术中肿瘤描绘。
To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors. The ability of dye-loaded polyacrylamide nanoparticles (NPs) containing methylene blue, Coomassie blue, or indocyanine green, to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells. Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent fashion. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3-targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin. F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.