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

• DOI: 10.1038/s41467-020-16814-4
• Publication Date: 2020-06-26T10:03:59Z
• Authors: F. J. Voskuil; P. J. Steinkamp; T. Zhao; B. van der Vegt; M. Koller; J. J. Doff; Y. Jayalakshmi; J. P. Hartung; J. Gao; B. D. Sumer; M. J. H. Witjes; G. M. van Dam; ; Y. Albaroodi; L. B. Been; F. Dijkstra; B. van Etten; Q. Feng; R. J. van Ginkel; K. Hall; K. Havenga; J. W. Haveman; P. H. J. Hemmer; L. Jansen; S. J. de Jongh; G. Kats-Ugurlu; W. Kelder; S. Kruijff; I. Kruithof; E. van Loo; J. L. N. Roodenburg; N. Shenoy; K. P. Schepman; S. A. H. J. de Vi...
• Keywords: Nanoprobe; Fluorescence-lifetime imaging microscopy; Indocyanine Green

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 translation of ONM-100, nanoparticle-based fluorescent imaging agent. This is comprised an ultra-pH sensitive amphiphilic polymer, conjugated with indocyanine green, which rapidly irreversibly dissociates fluoresce tumor due mechanism nanoscale macromolecular cooperativity. Primary outcomes were safety, pharmacokinetics feasilibity ONM-100. Secondary determine range safe doses ONM-100 intra-operative using commonly used fluorescence camera systems. In this study (Netherlands National Trial Register #7085), report that was well tolerated, four types could be visualized both in- ex vivo thirty subjects. enables detection tumor-positive resection margins 9/9 subjects additional otherwise missed occult lesions. Consequently, pH-activatable optical agent may clinically beneficial differentiating previously unexploitable narrow physiologic differences.