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

SHINE Study Grp, Voskuil, F. J., Steinkamp, P. J., Zhao, T., van der Vegt, B., Koller, M., Doff, J. J., Jayalakshmi, Y., Hartung, J. P., Gao, J., Sumer, B. D., Witjes, M. J. H. & van Dam, G. M., 1-Dec-2020, In : Nature Communications. 11, 1, p. 3257 10 p., 3257.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number3257
Pages (from-to)3257
Number of pages10
JournalNature Communications
Volume11
Issue number1
Publication statusPublished - 1-Dec-2020

    Keywords

  • CLINICAL-APPLICATIONS, HEAD

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