Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (${\text{Ca}}_{\mathrm{i}}^{2+}$) is a key cellular regulator, unraveling the ${\text{Ca}}_{\mathrm{i}}^{2+}$ 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 ${\text{Ca}}_{\mathrm{i}}^{2+}$ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three ${\text{Ca}}_{\mathrm{i}}^{2+}$ 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 ${\text{Ca}}_{\mathrm{i}}^{2+}$ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation.

微泡的超声超声可以局部增强药物递送，但微泡-细胞相互作用仍知之甚少。因为细胞内钙（${\text{钙}}_{\mathrm{我}}^{2+}$) 是一个关键的细胞调节器，解开 ${\text{钙}}_{\mathrm{我}}^{2+}$由振荡微泡引起的波动提供了对潜在生物效应的重要洞察。因此，我们开发了一种纳米和纳秒分辨率的光学成像系统，可以解决${\text{钙}}_{\mathrm{我}}^{2+}$波动和微泡振荡。使用这个系统，我们清楚地区分了三个${\text{钙}}_{\mathrm{我}}^{2+}$内皮细胞声穿孔后的摄取曲线，这与微泡振荡幅度、声穿孔的严重程度和细胞 - 细胞接触的打开密切相关。我们发现在没有致死细胞损伤的情况下可行药物递送的操作范围很窄。此外，相邻细胞受到以 15 μm/s 传播的钙波的影响。凭借独特的光学系统，我们揭示了药物输送所需的微泡振荡行为和${\text{钙}}_{\mathrm{我}}^{2+}$ 波动，提供对微泡-细胞相互作用的新见解，以帮助临床转化。