Cancer nanomedicine and the complement system activation paradigm: anaphylaxis and tumour growth

A wide variety of nanocarriers and particularly cancer nanomedicines activate the complement system, which is the first line of the innate immune defence mechanism. Complement activation may induce inflammatory responses, but such responses arising from uncontrolled complement activation could be life threatening. Accordingly, the role of complement in initiation of adverse reactions to particulate and polymer therapeutics is receiving increasing attention. Furthermore, the involvement of complement-activation products in promoting tumour growth has also been indicated. This could be of serious concern for development of cancer nanomedicines and cancer nanotechnology initiatives. These concepts are reviewed with preliminary evidence that intra-tumoural accumulation of model long circulating nanoparticles could promote tumour growth.