Lighting-Up Tumor for Assisting Resection via Spraying NIR Fluorescent Probe of γ-Glutamyltranspeptidas

Abstract

For the precision resection, development of near-infrared (NIR) fluorescent probe based on specificity identification tumor-associated enzyme for lighting-up the tumor area, is urgent in the field of diagnosis and treatment. Overexpression of γ-glutamyltranspeptidase, one of the cell-membrane enzymes, known as a biomarker is concerned with the growth and progression of ovarian, liver, colon and breast cancer compared to normal tissue. In this work, a remarkable enzyme-activated NIR fluorescent probe NIR-SN-GGT was proposed and synthesized including two moieties: a NIR dicyanoisophorone core as signal reporter unit; γ-glutamyl group as the specificity identification site. In the presence of γ-GGT, probe NIR-SN-GGT was transformed into NIR-SN-NH2, the recovery of Intramolecular Charge Transfer (ICT), liberating the NIR fluorescence signal, which was firstly employed to distinguish tumor tissue and normal tissues via simple “spraying” manner, greatly promoting the possibility of precise excision. Furthermore, combined with magnetic resonance imaging by T2 weight mode, tumor transplanted BABL/c mice could be also lit up for first time by NIR fluorescence probe having a large stokes, which demonstrated that probe NIR-SN-GGT would be a useful tool for assisting surgeon to diagnose and remove tumor in clinical practice.

Activity-based NIR fluorescent probes based on the versatile hemicyanine scaffold: design strategy, biomedical applications, and outlook

“…, cervical, breast, and liver cancer), and γ-GGT was also found to be involved in tumor progression and drug resistance of cancer cells. 260 As such, it is regarded as a biomarker for early diagnosis and prognostic evaluation of cancer. 261 Therefore, imaging of γ-GGT activity is vital for the diagnosis of related diseases.…”

Activity‐Based NIR Enzyme Fluorescent Probes for the Diagnosis of Tumors and Image‐Guided Surgery

“…Later, Peng and co‐workers devised the dicyanoisophorone‐based fluorescent probe NIR‐SN‐GGT for γ‐GGT (Figure 3 C). [44] The γ‐GGT induced the recognition group to undergo the hydrolysis reaction of the probe's amide bond, promptly generating the NIR fluorescence signal of 650 nm, which was ascribed to the recovery of the ICT mechanism. More importantly, when combined with magnetic resonance imaging (MRI), tumor‐transplanted mice could be visualized in situ by the simple spraying of probe NIR‐SN‐GGT (Figure 3 D), which indicated the availability of the probe to aid surgeons in removing tumors in clinical practice.…”

Activity‐based smart AIEgens for detection, bioimaging, and therapeutics: Recent progress and outlook

“…Fluorescent probe technology has been widely used to image biologically important substances (e.g., ions, signaling small molecules, and enzymes) in living cells and organisms for exploring the physiological and pathological processes of related diseases due to its intrinsic advantages of simplicity, convenience, high sensitivity, real-time, and noninvasiveness. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] With the popularity of multiphoton technology (two-/three-photon) and development of nearinfrared fluorescent dyes (especially near-infrared region II dyes, NIR II, 1000-1700 nm), we can directly observe the dynamic transformation process of some important active substances in deeper tissue and even in vivo, which can provide a comprehensive understanding of their important roles. [18][19][20][21] Interestingly, superresolution imaging of cells beyond the diffraction limit can be achieved through the combination of superresolution fluorescence microscopy and appropriate molecular probes.…”