title: Enzyme-Responsive Liposomes for the Delivery of Anticancer Drugs.
abstract: Liposomes are nanocarriers that deliver the payloads at the target site, leading to therapeutic drug concentrations at the diseased site and reduced toxic effects in healthy tissues. Several approaches have been used to enhance the ability of the nanocarrier to target the specific tissues, including ligand-targeted liposomes and stimuli-responsive liposomes. Ligand-targeted liposomes exhibit higher uptake by the target tissue due to the targeting ligand attached to the surface, while the stimuli-responsive liposomes do not release their cargo unless they expose to an endogenous or exogenous stimulant at the target site. In this review, we mainly focus on the liposomes that are responsive to pathologically increased levels of enzymes at the target site. Enzyme-responsive liposomes release their cargo upon contact with the enzyme through several destabilization mechanisms: (1) structural perturbation in the lipid bilayer, (2) removal of a shielding polymer from the surface and increased cellular uptake, (3) cleavage of a lipopeptide or lipopolymer incorporated in the bilayer, and (4) activation of a prodrug in the liposomes.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Fouladi
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Kristine J
authors.initials: KJ
authors.lastname: Steffen
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Sanku
authors.identifier: http://orcid.org/0000-0003-4236-2512
authors.initials: S
authors.lastname: Mallik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D055162:Biocatalysis; D002401:Cathepsin B / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D010196:Pancreatic Elastase / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D055666:Lipopeptides; D008081:Liposomes; D011108:Polymers; D011355:Prodrugs; D054497:Phospholipases A2, Secretory; D010196:Pancreatic Elastase; D014568:Urokinase-Type Plasminogen Activator; D017430:Prostate-Specific Antigen; D002401:Cathepsin B; D020782:Matrix Metalloproteinases