Department of Biomedical Engineering, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Biomedical Engineering, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ultrasound Med Biol. 2020 Aug;46(8):2017-2029. doi: 10.1016/j.ultrasmedbio.2020.03.029. Epub 2020 May 10.
Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble-cell interaction remains poorly understood. Because intracellular calcium (Ca) is a key cellular regulator, unraveling the Ca 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 Ca fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Ca 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 Ca fluctuations, providing new insight into the microbubble-cell interaction to aid clinical translation.
超声空化微泡可局部增强药物传递，但微泡-细胞相互作用仍知之甚少。由于细胞内钙（Ca）是细胞的关键调节因子，因此揭示由振荡微泡引起的 Ca 波动可为潜在的生物效应提供重要的见解。因此，我们开发了一种具有纳米和纳秒分辨率的光学成像系统，该系统可以解析 Ca 波动和微泡的振荡。使用该系统，我们在血管内皮细胞的声孔作用下清楚地区分了三种 Ca 摄取谱，这与微泡的振荡幅度、声孔作用的严重程度和细胞-细胞接触的开放强烈相关。我们发现了一个狭窄的工作范围，可在没有致命细胞损伤的情况下进行有效的药物传递。此外，相邻细胞受到以 15 μm/s 传播的钙波的影响。通过独特的光学系统，我们揭示了药物传递和 Ca 波动所需的微泡振荡行为，为微泡-细胞相互作用提供了新的见解，有助于临床转化。
