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Exploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery

Author

Listed:
  • F. J. Voskuil

    (University of Groningen, University Medical Center Groningen)

  • P. J. Steinkamp

    (University of Groningen, University Medical Center Groningen)

  • T. Zhao

    (OncoNano Medicine Inc.)

  • B. Vegt

    (University of Groningen, University Medical Center Groningen)

  • M. Koller

    (University of Groningen, University Medical Center Groningen)

  • J. J. Doff

    (University of Groningen, University Medical Center Groningen)

  • Y. Jayalakshmi

    (OncoNano Medicine Inc.)

  • J. P. Hartung

    (JPH Clinical Development)

  • J. Gao

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • B. D. Sumer

    (University of Texas Southwestern Medical Center)

  • M. J. H. Witjes

    (University of Groningen, University Medical Center Groningen)

  • G. M. Dam

    (University of Groningen, University Medical Center Groningen
    AxelaRx/TRACER B.V)

Abstract

Cancer cell metabolism leads to a uniquely acidic microenvironment in solid tumors, but exploiting the labile extracellular pH differences between cancer and normal tissues for clinical use has been challenging. Here we describe the clinical translation of ONM-100, a nanoparticle-based fluorescent imaging agent. This is comprised of an ultra-pH sensitive amphiphilic polymer, conjugated with indocyanine green, which rapidly and irreversibly dissociates to fluoresce in the acidic extracellular tumor microenvironment due to the mechanism of nanoscale macromolecular cooperativity. Primary outcomes were safety, pharmacokinetics and imaging feasilibity of ONM-100. Secondary outcomes were to determine a range of safe doses of ONM-100 for intra-operative imaging using commonly used fluorescence camera systems. In this study (Netherlands National Trial Register #7085), we report that ONM-100 was well tolerated, and four solid tumor types could be visualized both in- and ex vivo in thirty subjects. ONM-100 enables detection of tumor-positive resection margins in 9/9 subjects and four additional otherwise missed occult lesions. Consequently, this pH-activatable optical imaging agent may be clinically beneficial in differentiating previously unexploitable narrow physiologic differences.

Suggested Citation

  • F. J. Voskuil & P. J. Steinkamp & T. Zhao & B. Vegt & M. Koller & J. J. Doff & Y. Jayalakshmi & J. P. Hartung & J. Gao & B. D. Sumer & M. J. H. Witjes & G. M. Dam, 2020. "Exploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16814-4
    DOI: 10.1038/s41467-020-16814-4
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    Cited by:

    1. Meijie Pan & Ruiyang Zhao & Chuanxun Fu & Mingmei Tang & Jiayi Zhou & Bin Ma & Jianxiong Liu & Ye Yang & Binlong Chen & Qiang Zhang & Yiguang Wang, 2024. "Tuning nanoparticle core composition drives orthogonal fluorescence amplification for enhanced tumour imaging," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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