Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution
Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution
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DOI：
10.1021/mp800032f
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
McNeil, Scott E.
中科院分区：
文献类型：
--
作者：
Dobrovolskaia, Marina A.;Aggarwal, Parag;McNeil, Scott E.
纳米粒子具有独特的物理化学性质，这使它们成为很有前途的药物输送平台。然而，血液中的免疫细胞（如单核细胞、血小板、白细胞和树突状细胞）和组织中的免疫细胞（如常驻吞噬细胞）有吞噬和消除某些纳米颗粒的倾向。纳米颗粒与血浆蛋白（调理素）和血液成分（通过溶血、致血栓性和补体活化）的相互作用可能影响摄取和清除，因此可能影响到预期靶点的分布和递送。免疫细胞对纳米颗粒的摄取受多种因素的影响。不同的纳米颗粒已被证明作用于不同的途径，而不同的特征/性质也影响了颗粒内化的途径。一旦粒子进入生物介质，纳米粒子蛋白质结合几乎是瞬间发生的，而且这种粒子-蛋白质复合物的物理性质通常与配方粒子的物理性质不同。这些新特性有助于不同的生物反应和改变纳米颗粒的生物分布。因此，在不希望特异性递送到免疫细胞的情况下，理想的纳米粒子平台是在复杂的生物环境中完整性不受干扰的纳米粒子平台，它可以在血液中提供延长的循环以最大限度地递送到目标部位，对血液细胞成分无毒，并且对免疫细胞是“隐形的”，可以将其从循环中清除。这篇综述讨论了纳米颗粒与血液成分相互作用的最新数据，以及颗粒大小和表面电荷如何决定它们的血液相容性。这包括决定粒子与血浆蛋白相互作用和巨噬细胞摄取的特性。我们还将概述用于识别与免疫系统成分相互作用的体外方法，以及这种相互作用对颗粒分布到组织的潜在影响。
Nanoparticles have unique physicochemical properties which make them promising platforms for drug delivery. However, immune cells in the bloodstream (such as monocytes, platelets, leukocytes, and dendritic cells) and in tissues (such as resident phagocytes) have a propensity to engulf and eliminate certain nanoparticles. A nanoparticle's interaction with plasma proteins (opsonins) and blood components (via hemolysis, thrombogenicity and complement activation) may influence uptake and clearance and hence potentially affect distribution and delivery to the intended target sites. Nanoparticle uptake by the immune cells is influenced by many factors. Different nanoparticles have been shown to act on different pathways, while various characteristics/properties also affect which pathway is employed for particle internalization. Nanoparticle protein binding occurs almost instantaneously once the particle enters biological medium, and the physical properties of such a particle-protein complex are often different than those of the formulated particle. These new properties can contribute to different biological responses and change nanoparticle biodistribution. Therefore, in the situation when specific delivery to immune cells is not desired, the ideal nanoparticle platform is the one whose integrity is not disturbed in the complex biological environment, which provides extended circulation in the blood to maximize delivery to the target site, is not toxic to blood cellular components, and is "invisible" to the immune cells which can remove it from circulation. This review discusses the most recent data on nanoparticle interactions with blood components and how particle size and surface charge define their hematocompatibility. This includes properties which determine particle interaction with plasma proteins and uptake by macrophages. We will also provide an overview of in vitro methods useful in identifying interactions with components of the immune system and the potential effects of such interaction on particle distribution to tissues.