TY - JOUR
T1 - Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-Activatable near-Infrared fluorescent probe
AU - Wang, Lu
AU - Fan, Zhichao
AU - Zhang, Jingye
AU - Changyi, Yinzhi
AU - Huang, Cuiyun
AU - Gu, Yanjuan
AU - Xu, Ziyao
AU - Tang, Zhijia
AU - Lu, Weiyue
AU - Wei, Xunbin
AU - Li, Cong
PY - 2015/2/15
Y1 - 2015/2/15
N2 - 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.
AB - 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.
KW - Acidic tumor microenvironment
KW - Metastatic potential
KW - Near-infrared fluorescence
KW - Optical imaging
KW - PH responsive probe
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U2 - 10.1002/ijc.29153
DO - 10.1002/ijc.29153
M3 - Article
C2 - 25155456
AN - SCOPUS:84918816342
SN - 0020-7136
VL - 136
SP - E107-E116
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -