文献类型：期刊文献

英文题名：Highly Sensitive Hill-Type Small-Molecule pH Probe That Recognizes the Reversed pH Gradient of Cancer Cells

作者：Luo, Xiao[2];Yang, Haotian[3];Wang, Haolu[3];Ye, Zhiwei[4];Zhou, Zhongneng[5];Gu, Luyan[2];Chen, Jinquan[5];Xiao, Yi[4];Liang, Xiaowen[3];Qian, Xuhong[1,2];Yang, Youjun[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Univ Queensland, Translat Res Inst, Diamantina Inst, Therapeut Res Ctr, Woolloongabba, Qld 4102, Australia;[4]Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116024, Peoples R China;[5]East China Normal Univ, State Key Lab Precis Spect, Shanghai 200062, Peoples R China

年份：2018

卷号：90

期号：9

起止页码：5803

外文期刊名：ANALYTICAL CHEMISTRY

收录：;EI(收录号：20181905166306);WOS:【SCI-EXPANDED(收录号:WOS:000431464400040)】；

基金：The work is financially supported by the National Natural Science Foundation of China (Grant Nos. 21372080, 21572061, 21236002, and 11674101), the Fundamental Research Funds for the Central Universities (Grant Nos. WY1514053 and WY1516017), and the Australian National Health and Medical Research Council (Grant No. APP1122794).

语种：英文

外文关键词：Diseases - Probes - Molecules - Cells - pH - Synthesis (chemical) - Cytology

摘要：A hallmark of cancer cells is a reversed transmembrane pH gradient, which could be exploited for robust and convenient intraoperative histopathological analysis. However, pathologically relevant pH changes are not significant enough for sensitive detection by conventional Henderson-Hasselbalch-type pH probes, exhibiting an acid base transition width of 2 pH units. This challenge could potentially be addressed by a pH probe with a reduced acid-base transition width (i.e., Hill-type probe), appropriate pKa, and membrane permeability. Yet, a guideline to allow rational design of such small-molecule Hill-type pH probes is still lacking. We have devised a novel molecular mechanism, enabled sequential protonation with high positive homotropic cooperativity, and synthesized small-molecule pH probes (PHXI-3) with acid-base transition ranges of ca. 1 pH unit. Notably, PHX2 has a pKa of 6.9, matching the extracellular pH of cancer cells. Also, PHX2 is readily permeable to cell membrane and allowed direct mapping of both intra-and extracellular pH, hence the transmembrane pH gradient. PHX2 was successfully used for rapid and high contrast distinction of fresh unprocessed biopsies of cancer cells from normal cells and therefore has broad potentials for intraoperative analysis of cancer surgery.