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Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model.
Biomaterials ( IF 12.8 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.biomaterials.2020.119908
Mathilde Coustets 1 , Caroline Ladurantie 2 , Elisabeth Bellard 2 , Mélissa Prat 3 , Marie-Pierre Rols 2 , Vincent Ecochard 2 , Gwenaël Ferron 4 , Sophie Chabot 5 , Muriel Golzio 2 , Laurent Paquereau 2
Affiliation  

The epithelial ovarian cancer is one of the most lethal gynecological malignancy due to its late diagnostic and many relapses observed after first line of treatment. Once diagnose, the most important prognostic factor is the completeness of cytoreductive surgery. To achieve this goal, surgeons have to pinpoint and remove nodules, especially the smallest nodules. Recent advances in fluorescence-guided surgery led us to develop a recombinant lectin as a nanoprobe for the microscopic detection of nodules in the peritoneal cavity of tumor-bearing mice. This lectin has an intrinsic specificity for a carcinoma-associated glycan biomarker, the Thomsen-Friedenreich antigen. In this study, after its labelling by a near infrared dye, we first demonstrated that this nanoprobe allowed indirect detection of nodules already implanted in the peritoneal cavity, through tumor microenvironment targeting. Secondly, in a protocol mimicking the scattering of cells during surgery, we obtained a direct and long-lasting detection of tumor cells in vivo. This lectin as already been described as a nanocontainer able to do targeted delivery of a therapeutic compound to carcinoma cells. Future developments will focus on the combination of the nanoprobe and nanocontainer aspects in an intraperitoneal nanotheranostic approach.

中文翻译:

靶向Thomsen-Friedenreich抗原的近红外蛋白质纳米探针的开发,用于在手术中检测卵巢腹膜癌小鼠模型中的亚毫米结节。

上皮性卵巢癌是最致命的妇科恶性肿瘤之一,因为它的诊断较晚并且在一线治疗后观察到许多复发。一旦诊断,最重要的预后因素是减细胞手术的完整性。为了实现这一目标,外科医生必须查明并清除结节,尤其是最小的结节。荧光引导手术的最新进展使我们开发了一种重组凝集素,作为一种纳米探针,可用于显微镜检测荷瘤小鼠腹膜腔内的结节。该凝集素对癌相关的聚糖生物标记物Thomsen-Friedenreich抗原具有固有的特异性。在这项研究中,我们用近红外染料对其进行了标记,然后我们首先证明了这种纳米探针可以间接检测已经植入腹膜腔的结节,通过肿瘤微环境靶向。其次,在模拟手术过程中细胞散布的方案中,我们获得了体内肿瘤细胞的直接且持久的检测。该凝集素已经被描述为能够将治疗化合物靶向递送至癌细胞的纳米容器。未来的发展将集中在腹膜内纳米治疗方法中纳米探针和纳米容器方面的结合。
更新日期:2020-02-23
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