Plasma clearance of bacteriophage Qβ particles as a function of surface charge
Plasma clearance of bacteriophage Qβ particles as a function of surface charge
复制标题
DOI：
10.1021/ja075937f
复制
发表时间：
2008-01-30
影响因子：
15
通讯作者：
Finn, M. G.
中科院分区：
文献类型：
--
作者：
Prasuhn, Duane E., Jr.;Singh, Pratik;Finn, M. G.
自组装蛋白衣壳由于其单分散性和多功能的遗传和化学可定制性，作为一类有前景的生物医学纳米颗粒而受到关注。为了确定噬菌体 Q beta 多功能衣壳在小鼠中的血浆清除率和组织分布，使用 Cu-1 介导的叠氮-炔环加成反应用钆复合物修饰颗粒。内表面标记是通过首次将含叠氮化物的非天然氨基酸引入外壳蛋白而设计的。使用电感耦合等离子体发射光谱法通过定量检测 Gd 可以方便地监测清除率，并发现清除率与附着在颗粒外表面的复合物数量成反比。这种现象与生物共轭方案第一步中表面暴露的胺基酰化所引起的外表面电荷的变化相关。当通过叠氮-炔偶联重新引入伯胺基团时，循环时间相应增加。这些结果表明，纳米粒子的运输可以通过调节表面电荷的化学和遗传修饰以可预测的方式进行调整。
Self-assembled protein capsids have gained attention as a promising class of nanoparticles for biomedical applications due to their monodisperse nature and versatile genetic and chemical tailorability. To determine the plasma clearance and tissue distribution in mice of the versatile capsid of bacteriophage Q beta, the particles were decorated with gadolinium complexes using the Cu-1-mediated azide-alkyne cycloaddition reaction. Interior surface labeling was engineered by the introduction of an azide-containing unnatural amino acid into the coat protein for the first time. Clearance rates were conveniently monitored by quantitative detection of Gd using inductively coupled plasma optical emission spectroscopy and were found to be inversely proportional to the number of complexes attached to the exterior surface of the particle. This phenomenon was correlated to changes in exterior surface charge brought about by acylation of surface-exposed amine groups in the initial step of the bioconjugation protocol. When primary amine groups were reintroduced by azide-alkyne coupling, the circulation time increased accordingly. These results show that nanoparticle trafficking may be tailored in predictable ways by chemical and genetic modifications that modulate surface charge.