Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States.
Nano Lett. 2011 May 11;11(5):2178-82. doi: 10.1021/nl200862n. Epub 2011 Apr 20.
The future of genetic medicine hinges on successful intracellular delivery of nucleic acid-based therapeutics. While significant effort has concentrated on developing nanocarriers to improve the delivery aspects, scant attention has been paid to the synthetic process of poorly controlled nanocomplex formation. Proposed here is a reliable system to better control the complexation process, and thus the physical properties of the nanocomplexes, through microfluidics-assisted confinement (MAC) in picoliter droplets. We show that these homogeneous MAC-synthesized nanocomplexes exhibit narrower size distribution, lower cytotoxicity, and higher transfection efficiency compared to their bulk-synthesized counterparts. MAC represents a physical approach to control the energetic self-assembly of polyelectrolytes, thereby complementing the chemical innovations in nanocarrier design to optimize nucleic acid and peptide delivery.
基因医学的未来取决于核酸类治疗药物在细胞内的成功输送。虽然人们已经投入大量精力开发纳米载体以改善输送效果，但对纳米复合物形成这一难以控制的合成过程却关注甚少。本文提出了一种可靠的系统，即通过皮升级微流控限域（MAC）在微液滴中更好地控制复合物形成过程，从而控制纳米复合物的物理性质。我们发现，与批量合成的纳米复合物相比，这些通过均相 MAC 合成的纳米复合物具有更窄的粒径分布、更低的细胞毒性和更高的转染效率。MAC 代表了一种物理方法，可以控制聚电解质的能量自组装，从而与纳米载体设计中的化学创新相辅相成，以优化核酸和肽类的输送。
