Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-Activatable near-Infrared fluorescent probe

Lu Wang, Zhichao Fan, Jingye Zhang, Yinzhi Changyi, Cuiyun Huang, Yanjuan Gu, Ziyao Xu, Zhijia Tang, Weiyue Lu, Xunbin Wei, Cong Li

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-Associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distantorgan. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pHe) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors.

Original languageEnglish (US)
Pages (from-to)E107-E116
JournalInternational Journal of Cancer
Volume136
Issue number4
DOIs
StatePublished - Feb 15 2015
Externally publishedYes

Keywords

  • Acidic tumor microenvironment
  • Metastatic potential
  • Near-infrared fluorescence
  • Optical imaging
  • PH responsive probe

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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