Peptide modification is a popular strategy for developing an active targeting lipid nanoparticle (LNP). In modifying the surface of an LNP with a peptide, the sequence and structure of the peptide strongly affects the formation of the LNP. Specifically, a peptide with a high hydrophobicity can induce coarsening and aggregation of the LNP. In an attempt to prevent this from occurring, we incorporated monoacyl and diacyl group-conjugated poly(ethylene glycol) (PEG) into a LNP. We previously developed an original LNP, a multifunctional envelope type nanodevice (MEND) modified with an Epi-1 peptide, a ligand with a high affinity for the epithelial cell adhesion molecule (EpCAM). Using this peptide-modified MEND, the efficiency of delivery of a small interfering RNA (siRNA) encapsulated in the MEND was significantly improved. Although increasing the ratio of modification enhanced cellular uptake, the increase also induced aggregation of the LNP, particularly in the case of a large scale preparation. Our results indicate that a monoacyl PEG-lipid can prevent aggregation, even when the LNP is modified with higher molar ratios of peptide, but that this also results in a decrease in delivery efficiency. Moreover, the Epi-1-modified MEND exhibited a strong silencing effect in an ovarian cancer peritoneal dissemination model. Our results suggest that the simple incorporation of a monoacyl derivative into the PEG-lipid resulted in the formation of a peptide-modified LNP with improved characteristics.

中文翻译：

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PEG-单酰基脂肪酸制备的siRNA脂质纳米颗粒的稳定性提高，可促进配体介导的siRNA传递。

肽修饰是用于开发活性靶向脂质纳米颗粒（LNP）的流行策略。在用肽修饰LNP的表面时，肽的序列和结构强烈影响LNP的形成。具体地，具有高疏水性的肽可以诱导LNP的粗化和聚集。为了防止这种情况的发生，我们将单酰基和二酰基共轭的聚乙二醇（PEG）掺入了LNP中。我们以前开发了一种原始的LNP，一种经Epi-1肽修饰的多功能包膜型纳米器件（MEND），Epi-1肽是一种对上皮细胞粘附分子（EpCAM）具有高亲和力的配体。使用这种肽修饰的MEND，可以大大提高包裹在MEND中的小干扰RNA（siRNA）的递送效率。尽管增加修饰比例可提高细胞摄取，但增加也可诱导LNP聚集，特别是在大规模制备的情况下。我们的结果表明，即使用较高的肽摩尔比修饰LNP时，单酰基PEG-脂质也可以防止聚集，但这也导致递送效率降低。此外，Epi-1修饰的MEND在卵巢癌腹膜扩散模型中表现出强大的沉默效果。我们的结果表明，将单酰基衍生物简单地掺入PEG-脂质会导致形成具有改进特性的肽修饰LNP。我们的结果表明，即使用较高的肽摩尔比修饰LNP时，单酰基PEG-脂质也可以防止聚集，但这也导致递送效率降低。此外，Epi-1修饰的MEND在卵巢癌腹膜扩散模型中表现出强大的沉默效果。我们的结果表明，将单酰基衍生物简单地掺入PEG-脂质会导致形成具有改进特性的肽修饰LNP。我们的结果表明，即使用较高的肽摩尔比修饰LNP时，单酰基PEG-脂质也可以防止聚集，但这也导致递送效率降低。此外，Epi-1修饰的MEND在卵巢癌腹膜扩散模型中表现出强大的沉默效果。我们的结果表明，将单酰基衍生物简单地掺入PEG-脂质会导致形成具有改进特性的肽修饰LNP。