Department of Electronic Engineering, School of Electronic Science and Engineering, Xiamen University, Xiamen 361012, P. R. China.
School of Physics & Technology, Department of Clinical Laboratory, Institute of Medicine and Physics, Zhongnan Hospital, Renmin Hospital, Wuhan University, Wuhan 430072, P. R. China.
Anal Chem. 2024 Sep 17;96(37):14998-15007. doi: 10.1021/acs.analchem.4c03187. Epub 2024 Sep 6.
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 to 10 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.
细胞内货物输送对于药物评估、纳米医学发展和基因治疗至关重要，这些领域需要在保持细胞活力的同时实现高效率，以便进行下游分析。在这里，我们提出了一种声介导的精确药物输送机制，通过直接调节细胞微振动模式和细胞膜通透性来实现。通过基于相移键控的时空调控声镊，可以在摇摆势中实现可控的振荡细胞阵列。同时，持续施加于细胞的振荡辐射力和流体剪切力有效地干扰了细胞膜的流动性并增强了其通透性，从而促进了纳米药物的进入。在实验中，细胞的振动频率（10 到 10 Hz）、摇摆方向、幅度（0 到四分之一声波波长）和速度均可调节。阿霉素能够主动穿过细胞膜并在细胞内积累，浓度超过对照组的 8 倍以上。此外，在振荡过程中细胞活性没有明显降低，表现出优异的生物相容性。这种“跳舞声波”方案在时空域中引入了细胞操作的新维度和有效的药物输送策略，具有灵活性、温和性和高通量等优点。它可能会推动纳米生物学研究、药物和纳米医学发展以及医疗治疗等相关领域的发展。
