Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model

Abstract

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 2 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.

CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma

“…The exploitation of tumour specific and sensitive biomarkers represents a safe and noninvasive imaging modality to detect tumour progression and response to treatment. Imaging biomarkers VEGF and HER2 [8,9], FRa [10], Thomsen-Friedenreich glycan antigen [11] and EpCAM [12] for the detection of metastasised carcinomas have all shown potential in preclinical xenograft drug efficiency studies, as targeted therapeutics and potential targets to improve surgical resections in the intraoperative setting [13,14].…”

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents

“…To ensure the stability of the A38C tetramer structure, disulfide bonds were added in a crossover manner to prevent the dissociation of the oxidized A38C tetramer, and then, A38C was labeled with a NIR emission dye (alexa fluor 647) The final protein nanoprobe (A38C-alexa fluor 647) was obtained. 169 For cancer cells, the Thomsen−Friedenreich antigen is overexpressed, and A38C is able to specifically recognize it, a property that allows for enhanced targeting of A38C-alexa fluor 647 to tumor tissue. Finally, the investigators also evaluated the ability of A38C-alexa fluor 647 to detect submillimeter nodules in a mouse model of ovarian peritoneal carcinoma.…”

“…For example, Coustets et al developed a protein nanoprobe based on recombinant lectin protein (A38C) in 2020. To ensure the stability of the A38C tetramer structure, disulfide bonds were added in a crossover manner to prevent the dissociation of the oxidized A38C tetramer, and then, A38C was labeled with a NIR emission dye (alexa fluor 647) The final protein nanoprobe (A38C- alexa fluor 647) was obtained . For cancer cells, the Thomsen–Friedenreich antigen is overexpressed, and A38C is able to specifically recognize it, a property that allows for enhanced targeting of A38C-alexa fluor 647 to tumor tissue.…”