Detection of cancer cells using SapC-DOPS nanovesicles.
Detection of cancer cells using SapC-DOPS nanovesicles.
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DOI：
10.1186/s12943-016-0519-1
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发表时间：
2016-05-10
期刊：
影响因子：
37.3
通讯作者：
Qi X
中科院分区：
文献类型：
--
作者：
Davis HW;Hussain N;Qi X
与正常细胞不同，癌细胞在其细胞膜的细胞外小叶上表达高水平的磷脂酰丝氨酸。利用这一特性，我们的实验室开发了一种治疗剂，该治疗剂由融合蛋白saposin C（SapC）组成，其嵌入二油酰磷脂酰丝氨酸（DOPS）囊泡中。这些纳米囊泡选择性地靶向癌细胞并诱导细胞凋亡。在这里，我们回顾了支持使用SapC-DOPS定位肿瘤进行手术切除或治疗的数据。此外，有重要证据表明，SapC-DOPS也可能被证明是一种有效的新型癌症治疗试剂。鉴于SapC-DOPS很容易用亲脂性染料标记，它已与远红荧光染料CellVue Maroon（CVM）组合用于肿瘤靶向研究。我们还将造影剂纳入SapC-DOPS纳米囊泡中用于计算机断层扫描和磁共振成像，并在此处回顾这些数据。静脉内施用，荧光标记的SapC-DOPS穿过血脑肿瘤屏障，使得能够鉴定脑肿瘤。SapC-DOPS-CVM还在体内检测了多种其他小鼠肿瘤，使其可通过使用IVIS和多角度旋转光学成像的光学成像观察到。在30分钟内检测到染料，并在肿瘤内保留至少7天，而非肿瘤组织未染色（在肝脏中观察到的一些染料是一过性的，可能代表降解产物）。此外，标记的SapC-DOPS离体描绘了人组织学标本中的肿瘤。SapC-DOPS也可以用造影剂标记，用于计算机断层扫描或磁共振成像。总之，标记的SapC-DOPS提供了一种方便，特异性和无毒的方法来检测肿瘤，同时提供了治疗益处。
Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood–brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit.