Immunoglobulin deposition on biomolecule corona determines complement opsonization efficiency of preclinical and clinical nanoparticles.,Nature Nanotechnology

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Immunoglobulin deposition on biomolecule corona determines complement opsonization efficiency of preclinical and clinical nanoparticles.
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2019-01-14 , DOI: 10.1038/s41565-018-0344-3
Vivian P Vu ₁ , Geoffrey B Gifford ₁ , Fangfang Chen ₂ , Halli Benasutti ₁ , Guankui Wang _{1,

3} , Ernest V Groman _{1,

3} , Robert Scheinman ₃ , Laura Saba _{4,

5} , Seyed Moein Moghimi _{3,

6,

7} , Dmitri Simberg _{1,

3}

Affiliation

Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 opsonization, and may determine individual complement responses to nanomedicines.

中文翻译：

免疫球蛋白在生物分子电晕上的沉积决定了临床前和临床纳米颗粒的补体调理作用。

在纳米颗粒上沉积补体因子（调理作用）可能会促进巨噬细胞从血液中清除并触发促炎反应，但调节补体激活效率的机制了解甚少。我们先前证明，具有第三补体蛋白（C3）的超顺磁性氧化铁（SPIO）纳米蠕虫的调理作用取决于纳米颗粒的生物分子电晕。在这里，我们显示天然抗体在SPIO纳米蠕虫和一系列临床批准的纳米药物的C3调理素中起关键作用。C3调理作用对免疫球蛋白结合的依赖性几乎是普遍的，并且观察到与补体激活途径无关。仅需要几个表面结合的免疫球蛋白分子来触发补体激活和调理作用。尽管吸附在纳米颗粒上的血浆蛋白总量不能决定C3的沉积效率，但生物分子电晕本身可以增强免疫球蛋白与所有纳米颗粒类型的结合。因此，我们表明天然抗体代表生物分子电晕和C3调理作用之间的联系，并可能确定对纳米药物的个体补体反应。

更新日期：2019-01-15

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