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Cancer Res. 2019 Sep 1;79(17):4515-4523. doi: 10.1158/0008-5472.CAN-18-3337. Epub 2019 Jul 10.

DNA-SWCNT Biosensors Allow Real-Time Monitoring of Therapeutic Responses in Pancreatic Ductal Adenocarcinoma.

Author information

1
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Jacksonville, Florida.
2
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Jacksonville, Florida.
3
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
4
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Jacksonville, Florida. mukhopadhyay.debabrata@mayo.edu.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic cancer with limited treatment options. There is an urgent need for tools that monitor therapeutic responses in real time. Drugs such as gemcitabine and irinotecan elicit their therapeutic effect in cancer cells by producing hydrogen peroxide (H2O2). In this study, specific DNA-wrapped single-walled carbon nanotubes (SWCNT), which precisely monitor H2O2, were used to determine the therapeutic response of PDAC cells in vitro and tumors in vivo. Drug therapeutic efficacy was evaluated in vitro by monitoring H2O2 differences in situ using reversible alteration of Raman G-bands from the nanotubes. Implantation of the DNA-SWCNT probe inside the PDAC tumor resulted in approximately 50% reduction of Raman G-band intensity when treated with gemcitabine versus the pretreated tumor; the Raman G-band intensity reversed to its pretreatment level upon treatment withdrawal. In summary, using highly specific and sensitive DNA-SWCNT nanosensors, which can determine dynamic alteration of hydrogen peroxide in tumor, can evaluate the effectiveness of chemotherapeutics. SIGNIFICANCE: A novel biosensor is used to detect intratumoral hydrogen peroxide, allowing real-time monitoring of responses to chemotherapeutic drugs.

PMID:
31292162
PMCID:
PMC6726513
[Available on 2020-03-01]
DOI:
10.1158/0008-5472.CAN-18-3337

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