Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead
Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead
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DOI：
10.1016/j.jconrel.2010.04.003
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发表时间：
2010-09-01
影响因子：
10.8
通讯作者：
Szebeni, J.
中科院分区：
文献类型：
--
作者：
Moghimi, S. M.;Andersen, A. J.;Szebeni, J.
自问世以来，聚乙二醇磷脂(PEGPL)结合物在纳米药物控释系统的设计和工程中得到了广泛的应用，尤其是在非巨噬细胞靶标的药物控释系统中。然而，有报道称，在实验动物和人类中，某些聚乙二醇-磷脂工程纳米药物发生了特殊的反应。这些反应被归类为假过敏，可能与心肺功能障碍和其他相关过敏症状有关。最近的研究表明，补体激活可能是导致敏感个体对这种纳米药物的超敏反应的一个因素，但不是一个速度限制因素。这相当令人惊讶，因为聚乙二醇化结构通常被认为可以抑制蛋白质吸附和血液调理事件，包括补体。在这里，我们研究了聚乙二醇磷脂工程纳米药物和碳纳米管激活补体的分子基础，并讨论了未来的挑战。(C)2010爱思唯尔B.V.保留所有权利。
Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead. (C) 2010 Elsevier B.V. All rights reserved.