Matrix metalloproteinase-assisted triggered release of liposomal contents.
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.
Sarkar
Nihar
N
Department of Pharmaceutical Sciences North Dakota State University, Fargo, North Dakota 58105, USA.
Banerjee
Jayati
J
Hanson
Andrea J
AJ
Elegbede
Adekunle I
AI
Rosendahl
Theresa
T
Krueger
Aaron B
AB
Banerjee
Abir L
AL
Tobwala
Shakila
S
Wang
Rongying
R
Lu
Xiaoning
X
Mallik
Sanku
S
Srivastava
D K
DK
D000595:Amino Acid Sequence; D032701:Biomimetics; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D044366:Transition Temperature; D014357:Trypsin / Q000378:metabolism
D005456:Fluorescent Dyes; D008074:Lipoproteins; D008081:Liposomes; D010455:Peptides; D003094:Collagen; D014357:Trypsin; D020780:Matrix Metalloproteinase 9