Aptamer-displaying peptide amphiphile micelles as a cell-targeted delivery vehicle of peptide cargoes.
Aptamer-displaying peptide amphiphile micelles as a cell-targeted delivery vehicle of peptide cargoes.
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适体展示肽两亲胶束作为肽货物的细胞靶向递送载体。
DOI：
10.1088/1478-3975/aadb68
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发表时间：
2018
期刊：
影响因子：
2
通讯作者：
Ulery,BretD
中科院分区：
文献类型：
--
作者：
Smith,JosiahD;Cardwell,LeahN;Porciani,David;Nguyen,JulieA;Zhang,Rui;Gallazzi,Fabio;Tata,RamaRao;Burke,DonaldH;Daniels,MarkA;Ulery,BretD
肽两亲性胶束（PAMs）是用于递送各种治疗和预防性肽的有吸引力的载体。然而，PAM的一个关键限制是它们缺乏优先靶向能力。在本文中，我们描述了我们的PAM系统的设计，将DNA寡核苷酸两亲物（antitail两亲物-AA）形成A/PAMs。将具有与AA互补的3 '延伸序列（尾）的细胞靶向DNA适体退火至表面以形成适体展示PAM（适体~ A/PAM）。适体~ A/PAM是一种小的、阴离子的、稳定的纳米颗粒，与靶向DNA组分相比，能够递送大质量百分比的肽两亲物（PA）。适体~ A/PAM在生物体液中可稳定4 h以上。此外，适体在与A/PAM退火时保留其细胞靶向性质，从而导致向特异性靶向的B细胞白血病细胞系的递送增强。这种令人兴奋的模块化技术可以很容易地与不同靶向适体和PA的文库一起使用，能够提高肽货物的生物利用度和效力。
Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile—AA) to form A/PAMs. A cell-targeting DNA aptamer with a 3'extension sequence (tail) complementary to the AA is annealed to the surface to form aptamer-displaying PAMs (Aptamer~ A/PAMs). Aptamer~ A/PAMs are small, anionic, stable nanoparticles capable of delivering a large mass percentage peptide amphiphile (PA) compared to targeting DNA components. Aptamer~ A/PAMs are stable for over 4 h in the presence of biological fluids. Additionally, the aptamer retains its cell-targeting properties when annealed to the A/PAM, thus leading to enhanced delivery to a specifically-targeted B-cell leukemia cell line. This exciting modular technology can be readily used with a library of different targeting aptamers and PAs, capable of improving the bioavailability and potency of the peptide cargo.