Acoustic Controllable Spatiotemporal Cell Micro-oscillation for Noninvasive Intracellular Drug Delivery,Analytical Chemistry

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Acoustic Controllable Spatiotemporal Cell Micro-oscillation for Noninvasive Intracellular Drug Delivery
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-09-06 , DOI: 10.1021/acs.analchem.4c03187
Xiaoqi Gao _{1,

2,

3} , Dayang Li ₁ , Shukun Zhao _{2,

3} , Dongyong Yang ₄ , Qian Wu ₁ , Sen-Sen Li ₁ , Liyuan Zhang ₅ , Lu-Jian Chen ₁ , Yi Yang _{2,

3} , Xuejia Hu ₁

Affiliation

Intracellular cargo delivery is crucial for drug evaluation, nanomedicine development, and gene therapy, in which high efficiency while maintaining cell viability is needed for downstream analysis. Here, an acoustic-mediated precise drug delivering mechanism is proposed by directly modulating cell micro-oscillation mode and membrane permeability. Through phase shifting keying-based spatiotemporal acoustic tweezers, controllable oscillating cell arrays can be achieved in shaking potentials. At the same time, continually oscillating radiation force and fluid shear stress exerted on cells effectively disturbs cellular membrane mobility and enhances permeability, thereby facilitating nanodrug entrance. In experiments, cell oscillation is tunable in frequency (10^–2 to 10² Hz), shaking direction, amplitude (0 to quarter acoustic wavelength), and speed. Doxorubicin is actively delivered across cellular membranes and accumulates in inner cells, with a concentration more than 8 times that of the control group. Moreover, there is no obvious compromise in cell activity during oscillation, exhibiting excellent biocompatibility. This “dancing acoustic waves” scheme introduces a new dimension of cell manipulation in both space and time domains and an effective drug delivering strategy, offering advantages of flexibility, gentleness, and high throughput. It may advance related fields like nanobiological research, drug and nanomedicine development, and medical treatment.

中文翻译：

用于无创细胞内药物递送的声控时空细胞微振荡

细胞内货物递送对于药物评估、纳米药物开发和基因治疗至关重要，其中下游分析需要在保持细胞活力的同时实现高效率。在这里，通过直接调节细胞微振荡模式和膜通透性，提出了一种声介导的精确药物递送机制。通过基于相移键控的时空声镊，可以在震动电位中实现可控的振荡单元阵列。同时，施加在细胞上的持续振荡辐射力和流体剪切应力有效地干扰了细胞膜的流动性并增强了通透性，从而促进了纳米药物的进入。在实验中，细胞振荡在频率（^10-2 至 10² Hz）、振荡方向、振幅（0 至四分之一声波长）和速度方面可调。阿霉素主动跨细胞膜递送并在内细胞中积累，浓度是对照组的 8 倍以上。此外，在振荡过程中细胞活性没有明显影响，表现出优异的生物相容性。这种“跳舞声波”方案在空间和时间域中引入了细胞作的新维度以及有效的药物递送策略，具有灵活性、温和性和高通量等优点。它可能会推动纳米生物学研究、药物和纳米药物开发以及医学治疗等相关领域。

更新日期：2024-09-06

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