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

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 and G. M. Dam ()
Additional contact information
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
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

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16814-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16814-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16814-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().