Chemigenetic Far-Red Labels and Ca2+ Indicators Optimized for Photoacoustic Imaging.
J Am Chem Soc
; 146(34): 23963-23971, 2024 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-39158696
ABSTRACT
Photoacoustic imaging is an emerging modality with significant promise for biomedical applications such as neuroimaging, owing to its capability to capture large fields of view deep inside complex scattering tissue. However, widespread adoption of this technique has been hindered by a lack of suitable molecular reporters for this modality. In this work, we introduce chemigenetic labels and calcium sensors specifically tailored for photoacoustic imaging, using a combination of synthetic dyes and HaloTag-based self-labeling proteins. We rationally design and engineer far-red "acoustogenic" dyes, showing high photoacoustic turn-ons upon binding to HaloTag, and develop a suite of tunable calcium indicators based on these scaffolds. These first-generation photoacoustic reporters show excellent performance in tissue-mimicking phantoms, with the best variants outperforming existing sensors in terms of signal intensity, sensitivity, and photostability. We demonstrate the application of these ligands for labeling HaloTag-expressing neurons in mouse brain tissue, producing strong, specifically targeted photoacoustic signal, and provide a first example of in vivo labeling with these chemigenetic photoacoustic probes. Together, this work establishes a new approach for the design of photoacoustic reporters, paving the way toward deep tissue functional imaging.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Técnicas Fotoacústicas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos