Department of Chemical and Biomolecular Engineering , Tulane University , 6823 St. Charles Avenue , New Orleans , Louisiana 70118 , United States.
Department of Chemistry , Louisiana State University , Baton Rouge , Louisiana 70803 , United States.
Langmuir. 2019 Nov 26;35(47):15335-15343. doi: 10.1021/acs.langmuir.9b03322. Epub 2019 Nov 14.
Peptoids are highly biocompatible pseudopeptidic polyglycines with designable substituents on the nitrogen atoms. The therapeutic and drug-carrying potential of these materials requires a fundamental understanding of their interactions with lipid bilayers. In this work, we use amphiphilic polypeptoids with up to 100 monomeric units where a significant fraction (26%) of the nitrogen atoms are functionalized with decyl groups (hydrophobes) that insert into the lipid bilayer through the hydrophobic effect. These hydrophobically modified polypeptoids (HMPs) insert their hydrophobes into lipid bilayers creating instabilities that lead to the rupture of vesicles. At low HMP concentrations, such rupture leads to the creation of large fragments which remarkably anchor to intact vesicles through the hydrophobic effect. At high HMP concentrations, all vesicles rupture to smaller HMP-lipid fragments of the order of 10 nm. We show that the technique for such nanoscale polymer-lipid fragments can be exploited to sustain highly hydrophobic drug species in solution. Using the kinase inhibitor, Sorafenib as a model drug, it is shown that HMP-lipid fragments containing the drug can efficiently enter a hepatocellular carcinoma cell line (Huh 7.5), indicating the use of such fragments as drug delivery nanocarriers.
肽缩氨酸是高度生物相容的拟肽聚甘氨酸，其氮原子上具有可设计的取代基。这些材料的治疗和药物输送潜力需要对其与脂质双层的相互作用有基本的了解。在这项工作中，我们使用了长达 100 个单体单元的两亲性多肽缩氨酸，其中有 26%的氮原子被癸基（疏水分子）官能化，通过疏水作用插入脂质双层。这些疏水性修饰的多肽缩氨酸（HMP）将其疏水分子插入脂质双层中，产生不稳定性，导致囊泡破裂。在低 HMP 浓度下，这种破裂会导致形成大的片段，这些片段通过疏水作用显著地锚定在完整的囊泡上。在高 HMP 浓度下，所有的囊泡都会破裂成 10nm 左右的更小的 HMP-脂质片段。我们表明，可以利用这种纳米级聚合物-脂质片段的技术来稳定溶液中高度疏水的药物物质。以激酶抑制剂 Sorafenib 为模型药物，结果表明含有药物的 HMP-脂质片段能够有效地进入肝癌细胞系（Huh 7.5），这表明了这些片段可用作药物传递纳米载体。
