Red-emitting FIT-PNAs: “On site” detection of RNA biomarkers in fresh human cancer tissues

Dina Hashoul, Rachel Shapira, Maria Falchenko, Odelia Tepper, Vera Paviov, Aviram Nissan, Eylon Yavin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

To date, there are limited approaches for the direct and rapid visualization (on site)of tumor tissues for pathological assessment and for aiding cytoreductive surgery. Herein, we have designed FIT-PNAs (forced-intercalation-peptide nucleic acids)to detect two RNA cancer biomarkers. Firstly, a lncRNA (long noncoding RNA)termed CCAT1, has been shown as an oncogenic lncRNA over-expressed in a variety of cancers. The latter, an mRNA termed KRT20, has been shown to be over-expressed in metastases originating from colorectal cancer (CRC). To these FIT-PNAs, we have introduced the bis-quinoline (BisQ)cyanine dye that emits light in the red region (605–610 nm)of the visible spectrum. Most strikingly, spraying fresh human tissue taken from patients during cytoreductive surgery for peritoneal metastasis of colon cancer with an aqueous solution of CCAT1 FIT-PNA results in bright fluorescence in a matter of minutes. In fresh healthy tissue (from bariatric surgeries), no appreciable fluorescence is detected. In addition, a non-targeted FIT-PNA shows no fluorescent signal after spraying this FIT-PNA on fresh tumor tissue emphasizing the specificity of these molecular sensors. This study is the first to show on-site direct and immediate visualization of an RNA cancer biomarker on fresh human cancer tissues by topical application (spraying)of a molecular sensor.

Original languageAmerican English
Pages (from-to)271-278
Number of pages8
JournalBiosensors and Bioelectronics
Volume137
DOIs
StatePublished - 15 Jul 2019

Bibliographical note

Funding Information:
This work was supported by the Israel Science Foundation (grant No. 476/17 ) and the Israel Innovation Authority (grant No. 55330 ). We thank Prof. Abraham Rubinstein for his useful insights. EY acknowledges the David R. Bloom Center for Pharmacy and the Alex Grass Center for Drug Design and Novel Therapeutics for financial support.

Funding Information:
This work was supported by the Israel Science Foundation (grant No. 476/17)and the Israel Innovation Authority (grant No. 55330). We thank Prof. Abraham Rubinstein for his useful insights. EY acknowledges the David R. Bloom Center for Pharmacy and the Alex Grass Center for Drug Design and Novel Therapeutics for financial support.

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

  • CCAT1
  • Hyperthermic intraperitoneal chemotherapy
  • KRT20
  • Long non-coding RNA
  • Peptide nucleic acid

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