In Vivo Imaging of the Macrophage Migration Inhibitory Factor in Liver Cancer with an Activity-Based Probe

Abstract

The macrophage migration inhibitory factor (MIF), a vital cytokine and biomarker, has been suggested to closely associate with the pathogenesis of liver cancer. However, a simple and effective approach for monitoring the change and distribution of cellular MIF is currently lacking and urgently needed, which could be helpful for a better understanding of its role in the progression of cancer. Herein, we report a novel activity-based probe, TPP2, which allows for direct labeling and imaging of endogenous MIF activity within live cells, clinical tissues, and in vivo in a mouse model of liver cancer. With this probe, we have intuitively observed the dynamic change of intracellular MIF activity by both flow cytometry and confocal imaging. We further found that TPP2 permits the identification and distinguishing of liver cancer in vitro and in vivo with high sensitivity and selectivity toward MIF. Our observations indicate that TPP2 could provide a promising new imaging approach for elucidating the MIF-related biological functions in liver cancer.

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation

“…However, potential safety concerns may arise due to the high dosage of CNCI-1 for CT imaging. On the other hand, magnetic resonance (MR) imaging as a conventional imaging technology has been widely implemented in the clinic with the advantages of noninvasiveness, nonradioactivity, unlimited tissue penetration, and high spatial resolution. − Even so, MR imaging is still not sufficiently sensitive to detect tumor margins and unable to realize dynamic real-time monitoring due to inadequate specificity and unsatisfactory temporal resolution. , Meanwhile, NIRF imaging, a noninvasive, low-cost, and handy imaging technique with the advantages of high temporal resolution, sensitivity, and specificity, has been used to delineate and resect the tumors intraoperatively. − However, the limited tissue penetration depth and poor spatial resolution make NIRF imaging suffer from significant restrictions . Therefore, developing rational NIRF/MR multimodal imaging probes could help obtain comprehensive information on disease sites and aid surgeons in determining the margins of tumors with high accuracy and excising the tumor entirely.…”

Activity-Based Imaging of Macrophage Migration Inhibitory Factor with a Two-Photon Fluorescent Probe

“…Although we have successfully achieved imaging of MIF in cells via copper or non-copper-assisted click chemistry strategies, the requirement for a bio-toxic copper catalyst or the dependence on twostep labeling makes these probes somewhat limited in practical biological applications. 28,29 Other small-molecular probes that bind to MIF were also recently reported by the groups of Jorgensen and Dekker to be applied in screening studies of MIF inhibitors (Table S1), while these novel single-photon excited probes were not directly used for tracing the distribution of endogenous MIF in live cells or tissues. 30,31 Thus, developing simple and non-toxic activity-based probes to monitor MIF in living cells or pathological tissues is urgently needed to investigate the functions of MIF in biological systems.…”

“…Most of the reported assays mainly focus on in vitro indirect approaches, such as Western blot analysis, confocal immunofluorescence, immunohistochemistry, and so forth. , Activity-based probe sensing strategies allow real-time imaging of biomarkers in a non-invasive manner, providing a powerful approach for biomarker imaging due to their simplicity, high sensitivity, non-invasiveness, and low cost. − In our previous work, we developed a series of Woodward’s reagent K (WRK)-derived activity-based probes that show unique reactivity to catalytic N-terminal proline for specific labeling of MIF. Although we have successfully achieved imaging of MIF in cells via copper or non-copper-assisted click chemistry strategies, the requirement for a bio-toxic copper catalyst or the dependence on two-step labeling makes these probes somewhat limited in practical biological applications. , Other small-molecular probes that bind to MIF were also recently reported by the groups of Jorgensen and Dekker to be applied in screening studies of MIF inhibitors (Table S1), while these novel single-photon excited probes were not directly used for tracing the distribution of endogenous MIF in live cells or tissues. , Thus, developing simple and non-toxic activity-based probes to monitor MIF in living cells or pathological tissues is urgently needed to investigate the functions of MIF in biological systems.…”