Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Adv Healthc Mater. 2019 Mar;8(6):e1800996. doi: 10.1002/adhm.201800996. Epub 2018 Nov 22.
Protein- and peptide-based therapeutics with high tolerance and specificity along with low off-target effects and genetic risks have attracted tremendous attention over the last three decades. Herein, a new type of noncationic lipidoid nanoparticle (LNP) is reported for His-tagged protein delivery. Active lipidoids are synthesized by conjugating a nitrilotriacetic acid group with hydrophobic tails (EC16, O16B, and O17O) and nanoparticles are formulated in the presence of nickel ions and helper lipids (cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]). It is demonstrated that the newly developed LNPs are capable of delivering various His-tagged proteins including green fluorescent protein (GFP), (-30)GFP-Cre recombinase, and CRISPR/Cas9 ribonucleoprotein into mammalian cells.
在过去的三十年中，具有高耐受性和特异性、低脱靶效应和遗传风险的蛋白质和肽类治疗药物引起了极大的关注。在此，报道了一种新型的非阳离子脂质纳米颗粒（LNP）用于 His 标签蛋白的递药。活性脂质体是通过将氮川三乙酸基团与疏水尾部（EC16、O16B 和 O17O）偶联合成的，纳米颗粒是在镍离子和辅助脂质（胆固醇、1,2-二油酰基-sn-甘油-3-磷酸乙醇胺和 1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]）的存在下配制的。结果表明，新开发的 LNP 能够递送各种 His 标签蛋白，包括绿色荧光蛋白（GFP）、（-30）GFP-Cre 重组酶和 CRISPR/Cas9 核糖核蛋白进入哺乳动物细胞。
