The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson’s disease animals from healthy control mice in each instance.
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Rathnamalala, Chathuranga S. L. ; Hernandez, Selena ; Lucero, Melissa Y. ; Swartchick, Chelsea B. ; Kalam Shaik, Abdul ; Hammer, Nathan I. ; East, Amanda K. ; Gwaltney, Steven R. ; Chan, Jefferson ; Scott, Colleen N. ( , Angewandte Chemie International Edition)
Abstract Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400 nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near‐infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene (
SCR‐1 ), thienothiophene (SCR‐2 ), or bithiophene (SCR‐3 ). We leverage the fact thatSCR‐1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO (rNP‐NO ), which we employed to successfully visualize pathological levels of nitric oxide in a drug‐induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies. -
Rathnamalala, Chathuranga S. L. ; Hernandez, Selena ; Lucero, Melissa Y. ; Swartchick, Chelsea B. ; Kalam Shaik, Abdul ; Hammer, Nathan I. ; East, Amanda K. ; Gwaltney, Steven R. ; Chan, Jefferson ; Scott, Colleen N. ( , Angewandte Chemie)
Abstract Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400 nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near‐infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene (
SCR‐1 ), thienothiophene (SCR‐2 ), or bithiophene (SCR‐3 ). We leverage the fact thatSCR‐1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO (rNP‐NO ), which we employed to successfully visualize pathological levels of nitric oxide in a drug‐induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies. -
Yadav, Anuj K. ; Lee, Michael C. ; Lucero, Melissa Y. ; Su, Shengzhang ; Reinhardt, Christopher J. ; Chan, Jefferson ( , ACS Central Science)