Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

Abstract

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

Keywords: liposomes; solid tumor; surface functionalization; targeted drug delivery; targeting ligands.

Figure 1

Liposomes: Conventional liposomes are made of phospholipids (A); PEGylated/stealth liposomes contain a layer of polyethylene glycol (PEG) at the surface of liposomes (B); targeted liposomes contain a specific targeting ligand to target a cancer site (C); and multifunctional such as theranostic liposomes, which can be used for diagnosis and treatment of solid tumors (D).

Figure 2

Targets (extracellular and intracellular receptors or over-expressed proteins) for active drug targeting in cancer therapy. Targets may also be organelles, e.g., lysosomes and mitochondria.

Figure 3

Targets (receptors or over-expressed proteins) in tumor microenvironment or vasculature for active drug targeting in cancer therapy.

Figure 4

Surface functionalized liposome (summary) with various targeting ligands for enhanced delivery of payload at tumor site.