Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry
Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry
复制标题
DOI：
10.1021/acs.bioconjchem.6b00221
复制
发表时间：
2016-07-01
影响因子：
4.7
通讯作者：
Andresen, Thomas L.
中科院分区：
文献类型：
--
作者：
Bak, Martin;Jolck, Rasmus I.;Andresen, Thomas L.
纳米颗粒的功能化是提高药物递送系统对患病组织或细胞的特异性的关键要素。在目前的研究中，我们报告了一种高效和化学选择性的方法，用于脂质体与生物大分子的后功能化，这同样可以用于其他纳米颗粒或固体表面的功能化。该方法利用了在脂质体表面上具有亲和和共价锚定标签的协同效应。这是通过合成肽接头系统实现的，所述肽接头系统使用不含Cu的应变促进的点击化学与组氨酸亲和标签组合。用环状RGDfE肽进行PEG化脂质体的后官能化的研究。通过探索亲和标签和共价标签，实现了98 +/-2.0%的偶联效率，即使是稀释的系统也显示出87 +/-0.2%的偶联效率。通过HPLC定量反应动力学和总产率。这里提出的结果为构建复杂的纳米结构和功能化表面开辟了新的可能性。
Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well can be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry in combination with histidine affinity tags. The investigation of post-functionalization of PEGylated liposomes was performed with a cyclic RGDfE peptide. By exploring both affinity and covalent tags a 98 +/- 2.0% coupling efficiency was achieved, even a diluted system showed a coupling efficiency of 87 +/- 0.2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces.