Complement activation cascade triggered by PEG–PL engineered nanomedicines and carbon nanotubes: The challenges ahead

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. This article examines the molecular basis of complement activation by PEG–lipid engineered nanomedicines and other entities (e.g., PEGylated carbon nanotubes), highlighting the role of PEG-PL interfaces in modulating the activity of complement system, and discuss the challenges ahead. [Display omitted]