Biotin-tagged fluorescent sensor to visualize ‘mobile’ Zn²⁺ in cancer cells

Abstract

A cancer cell-targeting fluorescent sensor has been developed to image mobile Zn2+ by introducing a biotin group. It shows a highly selective response to Zn2+in vitro, no toxicity in cellulo and images 'mobile' Zn2+ specifically in cancer cells. We believe this probe has the potential to help improve our understanding of the role of Zn2+ in the processes of cancer initiation and development.

Protect to Detect: A Golgi Apparatus Targeted Probe to Image Mobile Zinc Through the Use of a Lipophilic Cell-Labile Protecting Group Strategy

“…The restriction of intramolecular rotations can also hinder the access to low energy conical intersections associated with ultrafast decay to the ground state. This theory was used to explain similar previous findings by us 6,22,31 and has been discussed elsewhere. 33,34…”

“…The trityl protected probe 1 was then readily obtained by stepwise double 'click' reactions following our originally reported procedures. 31 Although the deprotected probe 2 was ultimately ineffective in cellulo, as expected, it was also isolated for further characterization and testing in vitro. All products were satisfactorily characterized by 1 H, 13 C NMR and IR spectroscopies, as well as high-resolution mass spectrometry.…”

“…5, the fluorescence of 1 in HeLa cells increased significantly after the addition of zinc pyrithione, a membrane permeable zinc complex, indicating it has switch on fluorescence response to Zn 2+ in cellulo. When N,N,N',N'tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN), a well-known chelator of 'free' zinc, 31 was added, the fluorescence was almost completely quenched. Similar results were also observed in MCF-7 (Fig.…”

Subcellular localised small molecule fluorescent probes to image mobile Zn2+

“…In 2018, we developed the biotinylated probe 34 based on 1,8-naphthalimide moiety for imaging Zn 2+ in breast cancer MCF-7 cells and found it has nuclear envelope penetrability. 90 However, it suffers from the same issue as 33 in that it was distributed over the entire cell and its sensitivity was insufficient to detect endogenous nuclear Zn 2+ with the nucleus uorescence only being switched on aer the addition of exogenous Zn 2+ .…”

Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn2+ and identification of prostate cancer in human tissue

“…To date, considerable effort has been devoted to the development of Zn 2+ probes. [11][12][13][14][15][16][17][18][19][20] Fluorescence-based systems have received particular attention in this regard since they provide good sensitivity, selectivity, and spatial and temporal resolution. In 2010, Lippard, et al reported the uorescence Zn 2+ probe, ZPP1, which was successfully used to identify PCa in a transgenic mouse model.…”