摘要
Multispectral optoacoustic tomography (MSOT) is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the microscopic scale. While potential applications include the early detection of tumors below clinical thresholds set by current technology, the lack of tumor-specific contrast agents limits the use of MSOT imaging. Therefore, we constructed highly stable nano-contrast agents by coating gold nanorods (GNRs) with either polyacrylic acid (PAA) or amine- functionalized mesoporous silica (MS). Syndecan-1, which has been shown to target insulin-like growth factor 1 receptor (IGF1-R) (upregulated in pancreatic tumors), was conjugated on the surface of PAA-coated GNRs (PAA-GNRs) or MS-coated GNRs (MS-GNRs) to create tumor-targeted nanoparticles. In vitro, tumor targeting of nanoparticles was assessed with flow cytometry. In S2VP10L cells (positive for IGF1-R), the syndecan-1 MS-GNRs (Syndecan-MS-GNRs) demonstrated an increase in OA signal, 10x, compared to syndecan-1 PAA- GNRs (Syndecan-PAA-GNRs). Minimal binding was observed in MiaPaca-2 cells (negative for IGF1-R). In vivo, tumor specific targeting of Syndecan-MS-GNRs was evaluated using a murine orthotopic pancreatic cancer model. The Syndecan- MS-GNRs demonstrated significantly greater accumulation within pancreatic tumors than in off-target organs such as the liver. Mice implanted with the IGF1-R negative MiaPaca-2 cells did not demonstrate specific tumor targeting. In summary, we report that targeted nano-contrast agents (Syndecan-MS-GNRs) can successfully detect orthotopic pancreatic tumors with minimum off-target binding in vivo using MSOT.
Multispectral optoacoustic 断层摄影术(MSOT ) 是在传统的形式上提供几个优点的一种新兴的成像技术,特别地处于它解决在显微镜的规模上的深度的光对比的能力。当潜在的应用包括临床的阀值由当前的技术设置了的下面的肿瘤的早察觉时,肿瘤特定的对比代理人的缺乏限制 MSOT 成像的使用。因此,我们与 polyacrylic 酸(泛美航空公司) 或 aminefunctionalized mesoporous 硅石(MS ) 由涂层金牌 nanorods (GNR ) 构造了高度稳定的 nano 对比代理人。Syndecan-1,被显示了指向像胰岛素的生长因素 1 受体(IGF1-R )( 在胰腺的肿瘤的 upregulated ) ,在泛美航空公司涂的 GNR (PAA-GNRs ) 或 MS 涂的 GNR (MS-GNRs ) 的表面上被结合创造指向肿瘤的 nanoparticles。在 vitro, nanoparticles 指向的肿瘤与流动 cytometry 被估计。在 S2VP10L 房间(为 IGF1-R 积极) , syndecan-1 MS-GNRs (Syndecan-MS-GNRs ) 在 OA 信号表明了增加, 10x,与 syndecan-1 PAAGNR (Syndecan-PAA-GNRs ) 相比。最小的绑定在 MiaPaca-2 房间被观察(为 IGF1-R 否定) 。在 vivo,肿瘤 Syndecan-MS-GNRs 的特定的指向用鼠科的 orthotopic 被评估胰腺的癌症模型。Syndecan- MS-GNRs 比在象肝那样的离开目标机关在胰腺的肿瘤以内表明了显著地更大的累积。与 IGF1-R 否定 MiaPaca-2 房间植入的老鼠没表明指向的特定的肿瘤。在摘要,我们报导指向的 nano 对比代理人(Syndecan-MS-GNRs ) 能成功地检测 orthotopic 有在用 MSOT 的 vivo 有约束力的最小的离开目标的胰腺的肿瘤。