Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

An ideal drug carrier should have significant biocompatibility. The definition of biocompatibility pertaining to drug delivery systems has been concisely reviewed by Kohane and Langer. 41 A more comprehensive review by Naahidi et al. 42 emphasized that the ideal drug carrier should be devoid of intolerable toxic, thrombogenic, carcinogenic and immunogenic effects. The carrier should be sustained in the host long enough to carry out its intended function; therefore, the half-life of the carrier is an essential factor for ensuring its effectiveness. The delivery vehicle should be cleared from the biological system after performing its function without settling in any organs, which can lead to long-term side effects. The biocompatibility of a carrier nanoparticle is thus a relative property that depends on the risk-benefit ratio regarding its overall role without causing considerable damage to the body of the host. The suitability of the type of carrier used might vary from one context to another, but the end result should be an appropriate host response. 42 One of the major concerns associated with protein nanocarriers, which have repeated virus-like structural motifs, is their immunogenicity. Elevated Engineered protein cages in biomedical applications S Bhaskar and S Lim immunoglobulin G levels and B-cell numbers have been noted following a single dose of heat-shock protein and CPMV. 8 Multiple administrations could thus enhance immune responses and neutralize the carriers. Nanocarriers are cleared when they start to bind to proteins called opsonins, which mediate phagocytosis by the reticuloendothelial system of the host. 42 A common modality for reducing the immunogenic response would be to modify the carrier surface with poly(ethyleneglycol) (PEG), polymethylmethacrylate, poly (lactic-co-glycolic acid) or polyamidoamine. 3, 42 Alternative methods include coating with polyketals or glycan shielding. 8 Biodegradable carriers that are digested and cleaved by the body are often chosen over non-biodegradable ones, for they might cause toxic side effects. Such preferred carriers can be prepared from polysaccharides (e.g. chitosan), proteins, gelatin or biodegradable synthetic polymers such as poly(lactic-co-glycolic acid) and polylactic acid. 42 As they are made of proteins, protein nanocages are naturally biodegradable.