Complement: Alive and kicking nanomedicines

Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement system, giving rise to the release of anaphylatoxins C3a and C5a that initiate a wide array of responses through their effect on mast cells, polymorphonuclear cells, platelets and monocytes. Additionally, the terminal complement C5b-9 complex induces platelet activation, thereby enhancing their procoagulant activity, and has the capacity to elicit non-lytic stimulatory responses from vascular endothelial cells. Here we discuss the molecular basis of complement activation by liposomes, including poly(ethylene glycol) coated vesicles, and other related lipid-based and phospholipid-poly(ethylene glycol) conjugate stabilized entities. We have further considered the role of these complement activating entities in experimental oncology since intra-tumoural complement activation is suggested to induce tumour growth and progression.