A Conformationally Restricted Aza-BODIPY Platform for Stimulus-Responsive Probes with Enhanced Photoacoustic Properties

Effie Y. Zhou, Hailey J. Knox, Chang Liu, Weili Zhao, Jefferson Chan

Research output: Contribution to journalArticle

Abstract

Photoacoustic (PA) dyes, which absorb near-infrared (NIR) light to generate an ultrasonic signal, can be detected at centimeter depths in tissues with significantly higher resolution than dyes imaged with fluorescence-based methods. As such, PA agents show great promise as research tools for the study of live-animal disease models. However, the development of activatable PA probes has been hampered by the relative scarcity of appropriate PA-active molecular platforms with properties that can be manipulated in a rational manner. Herein we synthesized and evaluated six modifications to the aza-BODIPY dye platform with respect to their absorbance, fluorescence, and PA properties. We identified a promising conformationally restricted aza-BODIPY (CRaB) scaffold that prioritizes three criteria necessary for the design of stimulus-responsive dyes with optimal ratiometric PA response: absorbance at NIR wavelengths, strong PA intensity, and large Δλ upon interaction with the desired stimulus. Using this scaffold, we synthesized three chemically diverse stimulus-responsive PA probes and demonstrated between 2- and 8-fold improvements in theoretical ratiometric response in vitro. This suggests that improvements in PA parameters are generalizable. Finally, we validated the in vitro turnover of each CRaB PA probe and demonstrated the in vivo potential of the CRaB scaffold by direct comparison to an established hypoxia-responsive probe for the detection of tumor hypoxia.

Original languageEnglish (US)
Pages (from-to)17601-17609
Number of pages9
JournalJournal of the American Chemical Society
Volume141
Issue number44
DOIs
StatePublished - Nov 6 2019

Fingerprint

Photoacoustic effect
dye
Coloring Agents
probe
hypoxia
absorbance
near infrared
fluorescence
Fluorescence
Animal Disease Models
Dyes
Scaffolds
Ultrasonics
tumor
turnover
fold
wavelength
Light
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Infrared radiation

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

A Conformationally Restricted Aza-BODIPY Platform for Stimulus-Responsive Probes with Enhanced Photoacoustic Properties. / Zhou, Effie Y.; Knox, Hailey J.; Liu, Chang; Zhao, Weili; Chan, Jefferson.

In: Journal of the American Chemical Society, Vol. 141, No. 44, 06.11.2019, p. 17601-17609.

Research output: Contribution to journalArticle

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