期刊
MACROMOLECULAR BIOSCIENCE
卷 17, 期 1, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201600125
关键词
Cy5; Cy7; fluorescence resonance energy transfer; N-(2-hydroxypropyl)methacrylamide; near-infrared fluorescence
资金
- Department of Defense [W81XWH-13-1-0160]
Fluorescence resonance energy transfer (FRET) is applied to investigate the enzyme-responsive payload release from a macromolecular therapeutic. The donor Cy5 is attached to the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone and the acceptor Cy7 is bound to the termini of enzyme-sensitive peptide side chains. Upon exposure to an enzyme, the bond between the peptide and Cy7 is cleaved, thereby leading to the loss of FRET signal. This enzyme response is visualized at the cell, tissue and whole-body levels. The in vitro results demonstrate that high expression of cathepsin B in tumor cells induces effective release of the drug model from conjugates resulting in a high concentration of payload inside tumor cells. The in vivo and ex vivo images show that the conjugate releases drug model faster in the ovarian tumor than in the normal tissues. The information will enhance the understanding of enzyme-responsive polymer carriers and help to shape their design.
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