Quantitative Evaluation of Bioorthogonal Chemistries for Surface Functionalization of Nanoparticles
Quantitative Evaluation of Bioorthogonal Chemistries for Surface Functionalization of Nanoparticles
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DOI：
10.1021/bc3005057
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发表时间：
2012-12-01
影响因子：
4.7
通讯作者：
Andresen, Thomas L.
中科院分区：
文献类型：
--
作者：
Feldborg, Lise N.;Jolck, Rasmus I.;Andresen, Thomas L.
我们在此提出了一种基于羟胺和醛修饰脂质组分之间形成肟键的高效且化学选择性的脂质体功能化方法。我们对这种新方法与该领域其他最先进的缀合反应进行了系统和定量的比较。识别病变细胞上过度表达的受体或抗原的靶向脂质体在治疗和诊断应用中具有巨大的潜力。然而，通过后官能化方法对纳米粒子表面进行化学修饰的效果不如溶液中的有效，而且通常收率不高。此外，缀合效率通常很难表征，因此在许多报告中都没有得到解决。我们在此提出了一项对神经内分泌肿瘤靶向肽（TATE）功能化的聚乙二醇化脂质体的研究，该肽具有多种已用于纳米颗粒表面缀合的功能性。通过 HPLC 定量反应动力学和总产率。反应在溶液中以及通过脂质体的后功能化进行，以研究空间位阻的影响以及肽与脂质体表面之间可能的亲和力。这些研究证明了选择正确的化学方法以获得脂质体定量表面功能化的重要性。
We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.