Blending Low‐Frequency Vibrations and Push–Pull Effects Affords Superior Photoacoustic Imaging Agents

Abstract

Photoacoustic imaging (PAI), a state‐of‐the‐art noninvasive in vivo imaging technique, has been widely used in clinical disease diagnosis. However, the design of high‐performance PAI agents with three key characteristics, i.e., near‐infrared (NIR) absorption (λabs>800 nm), intense PA signals, and excellent photostability, remains a challenging goal. Herein, we present a facile but effective approach for engineering PAI agents by amplifying intramolecular low‐frequency vibrations and enhancing the push‐pull effect. As a demonstration of this blended approach, we constructed a PAI agent (BDP1‐NEt2) based on the boron‐dipyrromethene (BODIPY) scaffold. Compared with indocyanine green (ICG, an FDA‐approved organic dye widely utilized in PAI studies; λabs=788 nm), BDP1‐NEt2 exhibited a UV/Vis‐NIR spectrum peaked at 825 nm, superior in vivo PA signal intensity and outstanding stability to offer improved tumor diagnostics. We believe this work provides a promising strategy to develop the next generation of PAI agents.

Discovery of Natural Products Alleviating Renal Fibrosis with a Viscosity-Responsive Molecular Probe

“…BDP-KY was synthesized via the Knoevenagel condensation reaction, and its chemical structure was determined using 1 H NMR, 13 C NMR, and HRMS (Figures S1–S3). The probe was designed to bear a CF 3 group at the meso position, which could emit red-shifted fluorescence at the near-infrared region and respond to viscosity changes based on the rotation of CF 3 . , In a sticky medium, the rotation of CF 3 is restricted, which in turn limits the low-frequency vibrations within the molecule, leading to a decrease in nonradiative decay rate and fluorescence enhancement . We conducted molecular dynamics simulations to investigate the relationship between the structural and dynamical properties of BDP-KY and environmental viscosity (Figure B) .…”

“…30,31 In a sticky medium, the rotation of CF 3 is restricted, which in turn limits the low-frequency vibrations within the molecule, leading to a decrease in nonradiative decay rate and fluorescence enhancement. 32 We conducted molecular dynamics simulations to investigate the relationship between the structural and dynamical properties of BDP-KY and environmental viscosity (Figure 1B). 33 We examined three solutions of different viscosities, namely, water (1.01 cP) (Figure S4A), 50% glycerol (v/v) in water (6.00 cP) (Figure S4B), and 90% glycerol (v/v) in water (219 cP) (Figure S4C).…”

Design and Application of Fluorescent Probes to Detect Cellular Physical Microenvironments

“…Moreover, the incorporation of targeting groups enables BODIPY-based fluorescent molecular rotors to identify alterations in the viscosity of diverse organelles present in cells. − It is noteworthy that certain BODIPY molecules dissipate energy through the adoption of bending conformation in the excited state. As the ambient viscosity increases, the intramolecular bending becomes constrained and tends toward a planar structure, showing higher fluorescence quantum yields. − Thus, the behavior of the BODIPY fluorophore could be governed by multiple mechanisms, including TICT, the bending mechanism,and most likely their combination. , …”

Fluorescent small molecule donors

“…Photoacoustic (PA) tomography enables the imaging of biological tissues at centimeter depths using an NIR trigger and ultrasonic detection, providing accurate guidance for the treatment of cancer. 49–54 When combined with small molecule donors, deep tissue gas therapy can be readily monitored. The Chan group reported a NO donor based on PA (photoNODs).…”