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FRET Imaging of Enzyme‐Responsive HPMA Copolymer Conjugate
Author(s) -
Zhang Rui,
Yang Jiyuan,
Radford D. Christopher,
Fang Yixin,
Kopeček Jindřich
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201600125
Subject(s) - förster resonance energy transfer , conjugate , methacrylamide , chemistry , raft , in vivo , biophysics , cathepsin b , peptide , enzyme , ex vivo , in vitro , copolymer , fluorescence , biochemistry , polymer , biology , organic chemistry , mathematical analysis , acrylamide , physics , mathematics , microbiology and biotechnology , quantum mechanics
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.