High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles.
Ultrasound Med Biol
; 46(8): 2017-2029, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32402676
ABSTRACT
Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble-cell interaction remains poorly understood. Because intracellular calcium (Cai2+) is a key cellular regulator, unraveling the Cai2+ fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Cai2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai2+ uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cell-cell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 µm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai2+ fluctuations, providing new insight into the microbubble-cell interaction to aid clinical translation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Microbolhas
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article