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输送的声学可控时空细胞微振荡

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，其中下游分析需要高效率并同时保持细胞活力。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输送机制。通过基于相移键控的时空声学镊子，可以实现振荡电势的可控振荡单元阵列。同时，持续振荡的辐射力和流体剪切应力施加在细胞上，有效地扰乱细胞膜的流动性并增强渗透性，从而促进纳米药物的进入。在实验中，细胞振荡的频率（10 ^–2至 10 ² Hz）、振荡方向、振幅（0 至四分之一声波波长）和速度是可调的。阿霉素主动穿过细胞膜并在细胞内积聚，其浓度是对照组的 8 倍以上。此外，振荡过程中细胞活性没有明显受损，表现出优异的生物相容性。这种“舞蹈声波”方案引入了时空域细胞操作的新维度和有效的药物输送策略，具有灵活性、温和性和高通量的优势。它可能会推动纳米生物学研究、药物和纳米医学开发以及医疗等相关领域的发展。

更新日期：2024-09-06

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