The Mechanisms and Biomedical Applications of an NIR BODIPY-Based Switchable Fluorescent Probe

Abstract

Highly environment-sensitive fluorophores have been desired for many biomedical applications. Because of the noninvasive operation, high sensitivity, and high specificity to the microenvironment change, they can be used as excellent probes for fluorescence sensing/imaging, cell tracking/imaging, molecular imaging for cancer, and so on (i.e., polarity, viscosity, temperature, or pH measurement). In this work, investigations of the switching mechanism of a recently reported near-infrared environment-sensitive fluorophore, ADP(CA)2, were conducted. Besides, multiple potential biomedical applications of this switchable fluorescent probe have been demonstrated, including wash-free live-cell fluorescence imaging, in vivo tissue fluorescence imaging, temperature sensing, and ultrasound-switchable fluorescence (USF) imaging. The fluorescence of the ADP(CA)2 is extremely sensitive to the microenvironment, especially polarity and viscosity. Our investigations showed that the fluorescence of ADP(CA)2 can be switched on by low polarity, high viscosity, or the presence of protein and surfactants. In wash-free live-cell imaging, the fluorescence of ADP(CA)2 inside cells was found much brighter than the dye-containing medium and was retained for at least two days. In all of the fluorescence imaging applications conducted in this study, high target-to-noise (>5-fold) was achieved. In addition, a high temperature sensitivity (73-fold per Celsius degree) of ADP(CA)2-based temperature probes was found in temperature sensing.

A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging

“…With the stable ICG‐PNIPAM available, researchers recently reported in vivo USF imaging in a mouse for the first time . In addition, other USF contrast agents based on Pluronic micelles were also studied, showing a splendid performance with 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (aza‐BODIPY) dyes in a phantom model . However, the rapid degradation of these agents in biological environments should be addressed before they can be used for USF imaging in living tissues.…”

“…Second, compared to the ICG dye aqueous solution, the excitation peak of the ICG‐PNIPAM shifted from 788 to 660 nm and the emission peak changed from 809 to 690 nm . The aza‐BODIPY dye used in the micelle contrast agent has a similar excitation peak at 683 nm and an emission peak at 717 nm . For deep tissue USF imaging, an NIR contrast agent is desired to increase the photon penetration depth and minimize tissue autofluorescence .…”

Exploring NIR Aza-BODIPY-Based Polarity Sensitive Probes with ON-and-OFF Fluorescence Switching in Pluronic Nanoparticles

“…Recently, a new polarity-sensitive fluorophore was introduced, and its characteristics and application as a switchable fluorescent probe (SFP), when incorporated inside polymeric nanoparticles, were studied [11]. In this system, the heat generated from the focused ultrasound would increase the temperature of the tissue at the focus of the ultrasound.…”

Modulation of ultrasound-switchable fluorescence for improving signal-to-noise ratio

“…[1][2][3][4][5][6] We recently developed a new imaging method for deep-tissue high-resolution imaging, which has been termed as ultrasound-switchable fluorescence (USF). [7][8][9][10][11][12][13] It has been demonstrated that USF can simultaneously achieve high SNR (or sensitivity) and high spatial resolution in tissue with a depth of centimeters. [7][8][9][10][11][12][13] In this study, we report a new method to further improve the SNR (or sensitivity) of the USF imaging without sacrificing the spatial resolution by modulating the ultrasound exposure.…”

“…[7][8][9][10][11][12][13] It has been demonstrated that USF can simultaneously achieve high SNR (or sensitivity) and high spatial resolution in tissue with a depth of centimeters. [7][8][9][10][11][12][13] In this study, we report a new method to further improve the SNR (or sensitivity) of the USF imaging without sacrificing the spatial resolution by modulating the ultrasound exposure. The modulation parameters and data processing methods are also investigated and compared.…”