Near-Infrared Fluorescent Probes for the Detection of Cancer-Associated Proteases

Abstract

Proteases are enzymes capable of catalyzing protein breakdown, which is critical across many biological processes. There are several families of proteases, each of which perform key functions through the degradation of specific proteins. As our understanding of cancer improves, it has been demonstrated that several proteases can be overactivated during the progression of cancer and contribute to malignancy. Optical imaging systems that employ near-infrared (NIR) fluorescent probes to detect protease activity offer clinical promise, both for early detection of cancer as well as for the assessment of personalized therapy. In this Review, we review the design of NIR probes and their successful application for the detection of different cancer-associated proteases.

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

“…25–31 In particular, activity-based NIR fluorescent probes have gained attention due to their outstanding advantages in the field of detection and bioimaging. 32–34 These advantages include high specificity, good sensitivity, deep tissue penetration as well as a high signal-to-noise ratio, which can effectively prevent false positive signals. 35 However, due to the lack of an ideal fluorophore platform, smart NIR fluorescent probes are very challenging to fabricate.…”

Targeted Fluorogenic Cyanine Carbamates Enable In Vivo Analysis of Antibody–Drug Conjugate Linker Chemistry

“…While our previously reported sulfonated CyBams were not suitable for this application, the installation of a tertiary amine into the norcyanine framework dramatically improves cellular and in vivo signals, likely due to enhanced lysosomal uptake and retention. It is likely that these “lysotracker-like” norcyanines and the resulting CyLBam probes will have applications in other settings, including their use as activity-based sensing agents. , …”

“…It is likely that these "lysotracker-like" norcyanines and the resulting CyLBam probes will have applications in other settings, including their use as activity-based sensing agents. 61,62 In applying this approach for ADC applications, we assume that the fluorescent probe can serve as a useful surrogate for the payload component. Here we have shown that quantitative comparisons of linker chemistries can be obtained by varying the linker component.…”

Rational Design and Synthesis of Large Stokes Shift 2,6-Sulphur-Disubstituted BODIPYs for Cell Imaging

“…In recent years, our research group and others have focused on the preparation of several classes of fluorescent compounds [9][10][11][12][13][14][15][16]. Antitumor compounds with fluorescent properties, optical probes activated by enzymes [17][18][19][20][21][22], fluorescent amino acids and synthetic peptides for imaging studies [23][24][25][26][27][28][29][30], and more recently, boron-dipyrromethene (BODIPY) derivatives [31][32][33][34][35][36][37][38][39][40] have been the targets of many investigations.…”