Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
ACS Appl Mater Interfaces. 2020 Aug 12;12(32):35835-35844. doi: 10.1021/acsami.0c08268. Epub 2020 Jul 28.
Nanoparticles designed as messenger RNA (mRNA) carriers to deliver gene medicine have shown great potential to change the way lung disease states are managed. Controlling their delivery to the lung and the transgene expression in a specific population of cells remains a challenge. Here, we developed a series of nanoparticles with polyethylene glycol (PEG) corona prepared by condensing mRNA with PEG--polyethyleneimine (PEI--PEG) with different PEG terminal functional groups and grafting ratios. PEGylated nanoparticles (PEG grafting ratio was 0.5%) with amino or amino acid terminal groups showed the highest transgene expression levels in the lung following systemic administration, and cell profiling analysis indicated that pulmonary immune cells contributed to the majority of expression. We also showed that these nanoparticles can be prepared by the flash nanocomplexation method, which is a scalable and reproducible process, yielding lyophilizable nanoparticles that were stable for at least 4 months at -20 °C. These results suggest that these surface-functionalized PEGylated nanoparticles may serve as desirable carriers to deliver mRNA to the lung for pulmonary immunomodulation.
设计用于传递基因药物的信使 RNA（mRNA）载体的纳米颗粒，具有改变肺部疾病治疗方式的巨大潜力。然而，控制它们向肺部的传递以及在特定细胞群体中的转基因表达仍然是一个挑战。在这里，我们通过将 mRNA 与具有不同 PEG 端基官能团和接枝比的聚乙二醇-聚乙烯亚胺（PEI-PEG）缩合，开发了一系列具有聚乙二醇（PEG）冠的纳米颗粒。带有氨基或氨基酸端基的聚乙二醇化纳米颗粒（PEG 接枝率为 0.5%）在全身给药后，在肺部的转基因表达水平最高，细胞分析表明肺部免疫细胞是表达的主要贡献者。我们还表明，这些纳米颗粒可以通过闪蒸纳米复合方法制备，该方法是一种可扩展且可重复的过程，可得到冻干纳米颗粒，在-20°C 下至少稳定 4 个月。这些结果表明，这些表面功能化的聚乙二醇化纳米颗粒可能是将 mRNA 递送至肺部进行肺部免疫调节的理想载体。
