RESUMEN
A triggered release methodology of liposomal contents via the enzyme MMP-9 is described.
Asunto(s)
Liposomas/química , Metaloproteinasa 9 de la Matriz/química , Oligopéptidos/química , Proteínas de Artrópodos , Modelos BiológicosRESUMEN
Conjugation of surface binding groups with inhibitors for carbonic anhydrase leads to the conversion of weak inhibitors to strong inhibitors.
Asunto(s)
Inhibidores de Anhidrasa Carbónica/química , Histidina/química , Sulfonamidas/química , Unión Competitiva , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/metabolismo , Anhidrasas Carbónicas/metabolismo , Catálisis , Cinética , Metales Pesados/química , Metales Pesados/metabolismo , Modelos Químicos , Estructura Molecular , Compuestos Organometálicos/química , Compuestos Organometálicos/metabolismo , Unión Proteica , Sulfonamidas/síntesis química , Sulfonamidas/metabolismoRESUMEN
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.