ABSTRACT
We offer a novel methodology for formulating liposomes by incorporating sequence-specific collagen-mimetic peptides such that they are specifically "uncorked" by a matrix metalloproteinase, MMP-9. By encapsulating carboxyfluorescein (as a self-quenching fluorescent dye), we demonstrate that the time-dependent release of the dye from liposomes is due to the specific enzymatic cleavage of the surface-exposed collagen-mimetic peptides. The specificity of such cleavage is attested by the fact that the liposomal "uncorking" and their content release occur only by MMP-9 and not by a general proteolytic enzyme, trypsin, despite the fact that the collagen mimetic peptides contain the trypsin cleavage site. The mechanistic details underlying the formulations of liposomes and their enzyme-selective "uncorking" and content release are discussed. Arguments are presented that such liposomes can be fine-tuned to serve as the drug delivery vehicles for the detection and treatment of various human diseases, which occur due to the overexpression of a variety of pathogenic matrix metalloproteinases.
Subject(s)
Liposomes/chemistry , Liposomes/metabolism , Matrix Metalloproteinase 9/metabolism , Amino Acid Sequence , Biomimetics , Collagen/chemistry , Collagen/metabolism , Fluorescent Dyes/metabolism , Humans , Lipoproteins/chemistry , Lipoproteins/metabolism , Peptides/chemistry , Peptides/metabolism , Substrate Specificity , Time Factors , Transition Temperature , Trypsin/metabolismABSTRACT
A triggered release methodology of liposomal contents via the enzyme MMP-9 is described.
Subject(s)
Liposomes/chemistry , Matrix Metalloproteinase 9/chemistry , Oligopeptides/chemistry , Arthropod Proteins , Models, BiologicalABSTRACT
Conjugation of surface binding groups with inhibitors for carbonic anhydrase leads to the conversion of weak inhibitors to strong inhibitors.
