Development of Aptamer-Based Molecular Tools for Rapid Intraoperative Diagnosis and In Vivo Imaging of Serous Ovarian Cancer

ACS Appl Mater Interfaces. 2021 Apr 14;13(14):16118-16126. doi: 10.1021/acsami.1c02072. Epub 2021 Mar 31.

Abstract

Diagnosis and treatment of ovarian cancer are based on intraoperative pathology and debulking surgery. The development of a novel molecular tool is significant for rapid intraoperative pathologic diagnosis, which instructs the decision-making on excision surgery and effective chemotherapy. In this work, we represent a DNA aptamer named mApoc46, which is generated from cell-SELEX by targeting patient-derived primary serous ovarian cancer (pSOC) cells. An average dissociation constant (Kd) was determined to be 0.15 ± 0.05 μM by flow cytometry. The mApoc46 aptamer displays a robust specificity to pSOC cells. Labeled with FAM, mApoc46 can selectively stain living pSOC cells in 30 min without staining commercial OC cell lines and cell lines associated with other cancers. Interestingly, FAM-mApoc46 displayed superb selectivity toward high-grade serous ovarian cancer (HG-SOC) tissues in frozen sections against low-grade SOC, ovarian borderline tumor, other nonepithelial ovarian tumors, and healthy ovarian tissue. These results lead to a potential application in the identification of OCs' histological subtypes during operation. In the patient-derived tumor xenograft NCG mice model, Cy5-labeled mApoc46 was found to accumulate at the tumor area and served as an in vivo imaging probe. The mApoc46 probe shows a robust and stable performance to visualize SOC tumors in the body. Therefore, aptamer mApoc46 holds great potential in rapid intraoperative detection, pathological diagnosis, fluorescence image-guided cancer surgery, and targeted drug delivery and therapy.

Keywords: aptamer; cell-SELEX; intraoperative pathological diagnosis; molecular tool; serous ovarian cancer.

MeSH terms

  • Animals
  • Aptamers, Nucleotide*
  • Female
  • Heterografts
  • Humans
  • Intraoperative Period
  • Mice
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / diagnostic imaging
  • SELEX Aptamer Technique

Substances

  • Aptamers, Nucleotide