4.8 Article

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

Journal

SCIENCE ADVANCES
Volume 4, Issue 4, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaq1090

Keywords

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Funding

  1. NIH New Innovator Award [DP2-HD075698]
  2. NIH Cancer Center Support Grant [P30 CA008748]
  3. Honorable Tina Brozman Foundation for Ovarian Cancer Research
  4. Louis V. Gerstner Jr. Young Investigator's Fund
  5. Frank A. Howard Scholars Program
  6. Alan and Sandra Gerry Metastasis Research Initiative
  7. Center for Molecular Imaging and Nanotechnology at MSKCC
  8. Cycle for Survival
  9. Anna Fuller Fund
  10. Commonwealth Foundation for Cancer Research
  11. Imaging and Radiation Sciences Program
  12. Experimental Therapeutics Center at MSKCC
  13. Ovarian Cancer Research Fund (Ann Schreiber Mentored Investigator Award) [370463]
  14. American Heart Association Postdoctoral Fellowship [17POST33650043]
  15. Frank Lappin Horsfall Jr. Fellowship
  16. Hunter R. Rawlings III Cornell Presidential Research Scholars program
  17. Gerstner Sloan Kettering Summer Undergraduate Research Program
  18. U.S. Department of Defense [W81XWH-11-2-0230, W81XWH-15-1-0429]

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Patients with high-grade serous ovarian carcinoma ( HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The U.S. Food and Drug Administration-approved biomarkers for HGSC-CA-125 (cancer antigen 125) and HE4 (human epididymis protein 4)-do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease.

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