Evolution of liposomes. (A) Early conventional ‘plain’ phospholipid liposomes with water-soluble drug (a) entrapped within the aqueous liposome interior, and water-insoluble drug (b) incorporated in the liposomal membrane. (B) Long-circulating liposome grafted with a protective polymer (c) such as polyethylene glycol (PEG), which shields the liposome surface from the interaction with opsonizing proteins. (C) Antibody-targeted immunoliposome with antibody covalently coupled (d) to the reactive phospholipids in the membrane, or hydrophobically anchored (e) in the liposomal membrane after preliminary modification with a hydrophobic moiety. (D) Long-circulating immunoliposome simultaneously bearing both a protective polymer and an antibody (f) or, preferably, antibody bound to the distal end of a grafted polymeric chain (g). (E) “Smart” liposome, the surface of which can be modified (separately or simultaneously) by the incorporation of stimuli-sensitive lipids such as temperature, pH, reduction sensitive lipids (h); modification with a detachable stimuli-sensitive protective polymer (i) or modification with a detachable stimuli-sensitive protective polymer with a targeting ligand such as an antibody attached to the distal tip of the polymer (j); loading with magnetic particles (k) for magnetic targeting. Republished with permission of [Royal Society of Chemistry], from [Liposomes as ‘smart’ pharmaceutical nanocarriers, Sawant, R.R. and Torchilin, V.P., 6, 17, 2010] [14]; permission conveyed through Copyright Clearance Center, Inc.