Wang Zeyu, Rich Joseph, Hao Nanjing, Gu Yuyang, Chen Chuyi, Yang Shujie, Zhang Peiran, Huang Tony Jun
Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708 USA.
Department of Biomedical Engineering, Duke University, Durham, NC 27708 USA.
Microsyst Nanoeng. 2022 Apr 28;8:45. doi: 10.1038/s41378-022-00374-2. eCollection 2022.
Nanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects. However, the development of exosome-encapsulated drug nanocarriers is limited by low drug loading efficiencies and/or complex, time-consuming drug loading processes. Herein, we have developed an acoustofluidic device that simultaneously performs both drug loading and exosome encapsulation. By synergistically leveraging the acoustic radiation force, acoustic microstreaming, and shear stresses in a rotating droplet, the concentration, and fusion of exosomes, drugs, and porous silica nanoparticles is achieved. The final product consists of drug-loaded silica nanocarriers that are encased within an exosomal membrane. The drug loading efficiency is significantly improved, with nearly 30% of the free drug (e.g., doxorubicin) molecules loaded into the nanocarriers. Furthermore, this acoustofluidic drug loading system circumvents the need for complex chemical modification, allowing drug loading and encapsulation to be completed within a matter of minutes. These exosome-encapsulated nanocarriers exhibit excellent efficiency in intracellular transport and are capable of significantly inhibiting tumor cell proliferation. By utilizing physical forces to rapidly generate hybrid nanocarriers, this acoustofluidic drug loading platform wields the potential to significantly impact innovation in both drug delivery research and applications.
已发现纳米载体和外泌体包封可显著提高靶向药物递送的功效，同时还能将不良副作用降至最低。然而，外泌体包封的药物纳米载体的开发受到低药物负载效率和/或复杂、耗时的药物负载过程的限制。在此，我们开发了一种声流体装置，可同时进行药物负载和外泌体包封。通过协同利用旋转液滴中的声辐射力、声微流和剪切应力，实现了外泌体、药物和多孔二氧化硅纳米颗粒的浓缩和融合。最终产物为由外泌体膜包裹的载药二氧化硅纳米载体。药物负载效率显著提高，近30%的游离药物（如阿霉素）分子被负载到纳米载体中。此外，这种声流体药物负载系统无需复杂的化学修饰，可在几分钟内完成药物负载和包封。这些外泌体包封的纳米载体在细胞内运输中表现出优异的效率，能够显著抑制肿瘤细胞增殖。通过利用物理力快速生成混合纳米载体，这种声流体药物负载平台有望对药物递送研究和应用的创新产生重大影响。
