A de novo strategy to develop NIR precipitating fluorochrome for long-term in situ cell membrane bioimaging
- 18 February 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (8)
- https://doi.org/10.1073/pnas.2018033118
Abstract
Cell membrane–targeted bioimaging is a prerequisite for studying the roles of membrane-associated biomolecules in various physiological and pathological processes. However, long-term in situ bioimaging on the cell membrane with conventional fluorescent probes leads to diffusion into cells from the membrane surface. Therefore, we herein proposed a de novo strategy to construct an antidiffusion probe by integrating a fluorochrome characterized by strong hydrophobicity and low lipophilicity, with an enzyme substrate to meet this challenge. This precipitating fluorochrome HYPQ was designed by conjugating the traditionally strong hydrophobic solid-state fluorochrome 6-chloro–2-(2-hydroxyphenyl) quinazolin-4(3H)-one (HPQ) with a 2-(2-methyl–4H-chromen–4-ylidene) malononitrile group to obtain closer stacking to lower lipophilicity and elongate emission to the far-red to near-infrared wavelength. As proof-of-concept, the membrane-associated enzyme γ-glutamyltranspeptidase (GGT) was selected as a model enzyme to design the antidiffusion probe HYPQG. Then, benefiting from the precipitating and stable signal properties of HYPQ, in situ imaging of GGT on the membrane was successfully realized. Moreover, after HYPQG was activated by GGT, the fluorescence signal on the cell membrane remained unchanged, with incubation time even extending to 6 h, which is significant for in situ monitoring of enzymatic activity. In vivo testing subsequently showed that the tumor region could be accurately defined by this probe after long-term in situ imaging of tumor-bearing mice. The excellent performance of HYPQ indicates that it may be an ideal alternative for constructing universal antidiffusion fluorescent probes, potentially providing an efficient tool for accurate imaging-guided surgery in the future.Keywords
Funding Information
- National Natural Science Foundation of China (21977027)
- National Natural Science Foundation of China (21890744)
- National Natural Science Foundation of China (22074036)
- The National Key R&D Program of China (2019YFA0210100)
- National Natural Science Foundation of China (21804068)
- the National Postdoctoral Program for Innovative Talents (BX20190110)
- Hunan Provincial Innovation Foundation for Postgraduate (CX2018B189)
This publication has 57 references indexed in Scilit:
- Anticancer effects of sodium butyrate on hepatocellular carcinoma cells in vitroInternational Journal of Molecular Medicine, 2013
- Cell‐surface sensors: lighting the cellular environmentWIREs Nanomedicine and Nanobiotechnology, 2012
- Polymorph‐Dependent Solid‐State Fluorescence and Selective Metal‐Ion‐Sensor Properties of 2‐(2‐Hydroxyphenyl)‐4(3H)‐quinazolinoneChemistry – An Asian Journal, 2011
- Rapid Cancer Detection by Topically Spraying a γ-Glutamyltranspeptidase–Activated Fluorescent ProbeScience Translational Medicine, 2011
- A novel procedure for routine milk fat extraction based on dichloromethaneJournal of Food Composition and Analysis, 2010
- Expression of γ-glutamyltransferase in cancer cells and its significance in drug resistanceBiochemical Pharmacology, 2006
- Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cellsJournal of Lipid Research, 2005
- Extraordinary hyperconjugation of the methyl group in the S1 state of 8‐methylquinolineLuminescence, 2001
- Extracellular glutathione is a source of cysteine for cells that express .gamma.-glutamyl transpeptidaseBiochemistry, 1993
- Sodium butyrate enhances the activities of membranal enzymes and increases drug sensitivity in a cell line from ascitic fluid of an ovarian carcinoma patientEuropean Journal of Cancer and Clinical Oncology, 1989