Mulvey J Justin, Feinberg Evan N, Alidori Simone, McDevitt Michael R, Heller Daniel A, Scheinberg David A
Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Tri-Institutional MD-PhD Program, New York, NY, USA.
Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA ; Department of Applied Physics, Yale University, New Haven, CT USA.
Int J Nanomedicine. 2014 Sep 4;9:4245-55. doi: 10.2147/IJN.S66050. eCollection 2014.
We aimed to create a more robust and more accessible standard for amine-modifying single-walled carbon nanotubes (SWCNTs). A 1,3-cycloaddition was developed using an azomethine ylide, generated by reacting paraformaldehyde and a side-chain-Boc (tert-Butyloxycarbonyl)-protected, lysine-derived alpha-amino acid, H-Lys(Boc)-OH, with purified SWCNT or C60. This cycloaddition and its lysine adduct provides the benefits of dense, covalent modification, ease of purification, commercial availability of reagents, and pH-dependent solubility of the product. Subsequently, SWCNTs functionalized with lysine amine handles were covalently conjugated to a radiometalated chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The (111)In-labeled construct showed rapid renal clearance in a murine model and a favorable biodistribution, permitting utility in biomedical applications. Functionalized SWCNTs strongly wrapped small interfering RNA (siRNA). In the first disclosed deployment of thermophoresis with carbon nanotubes, the lysine-modified tubes showed a desirable, weak SWCNT-albumin binding constant. Thus, lysine-modified nanotubes are a favorable candidate for medicinal work.
我们旨在为胺修饰的单壁碳纳米管（SWCNT）创建一个更强大且更易于使用的标准。利用由多聚甲醛与侧链-叔丁氧羰基（Boc）保护的赖氨酸衍生的α-氨基酸H-Lys（Boc）-OH反应生成的甲亚胺叶立德，与纯化的SWCNT或C60进行1,3-环加成反应。这种环加成反应及其赖氨酸加合物具有密集共价修饰、易于纯化、试剂可商购以及产物pH依赖性溶解性等优点。随后，用赖氨酸胺处理功能化的SWCNT与放射性金属螯合剂1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）共价缀合。在小鼠模型中，（111）In标记的构建体显示出快速的肾脏清除率和良好的生物分布，可用于生物医学应用。功能化的SWCNT能强烈包裹小干扰RNA（siRNA）。在首次公开的碳纳米管热泳应用中，赖氨酸修饰的碳纳米管显示出理想的、较弱的SWCNT-白蛋白结合常数。因此，赖氨酸修饰的纳米管是药物研究的理想候选物。
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