Peptide amphiphile micelles (PAMs) are a powerful platform technology for improving the delivery of therapeutic and prophylactic peptides. While previous research has shown aptamer-displaying PAMs enhance cell association, transportation to intracellular targets still remains a substantial hurdle for these biomaterials. In this article, we detail our efforts to address this challenge through the creation of disulfide-linked peptide amphiphile (PAs). These molecules were found to self-assemble in water into PAMs for which lipidated DNA oligomers (i.e., antitail amphiphiles – AAs) could be entrapped and used to tether aptamers (Apt) to the nanoparticle surface. These Apt∼A/PAMs were physically characterized and evaluated for their blood-serum stability using fetal bovine serum exposure and glutathione reduction. To assess their enhanced intracellular delivery capacity and therapeutic functionality, PAMs bearing cell-penetrating peptide modified “Plenty of SH3 domains” scaffold protein competitive inhibitor (Tat-POSH) and B cell lymphoma targeting aptamer (C10.36) were incubated with Ramos cells, a non-Hodgkin lymphoma cell line. C10.36∼A/PAMs were found not only to be stable in blood-like conditions, but also to be capable of facilitating delivery of therapeutic Tat-POSH peptide to Ramos cells in vitro.

中文翻译：

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通过展示适体，二硫键连接的肽两亲胶束的治疗性肽递送

肽两亲胶束（PAM）是用于改善治疗性肽和预防性肽的递送的强大平台技术。尽管先前的研究表明，展示适体的PAM增强了细胞结合，但向这些生物材料的细胞内靶标运输仍然是一大障碍。在本文中，我们详细介绍了通过创建二硫键连接的肽两亲物（PA）来应对这一挑战的努力。发现这些分子可在水中自组装成PAM，其脂质化的DNA寡聚物（即可以截留抗尾两亲物（AA），并将其用于将适体（Apt）束缚在纳米颗粒表面。对这些Apt-A / PAMs进行物理表征，并通过胎牛血清暴露和谷胱甘肽还原来评估它们的血清稳定性。为了评估其增强的细胞内递送能力和治疗功能，将带有细胞穿透肽修饰的“ SH3结构域大量”支架蛋白竞争性抑制剂（Tat-POSH）和B细胞淋巴瘤靶向适体（C10.36）的PAM与Ramos细胞孵育，非霍奇金淋巴瘤细胞系。发现C10.36〜A / PAMs不仅在血样条件下稳定，而且还能够促进治疗性Tat-POSH肽向体外Ramos细胞的递送。