Protease-activatable cell-penetrating peptide possessing ROS-triggered phase transition for enhanced cancer therapy

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Reactive oxygen species (ROS)- or protease-responsive materials have been utilized as carriers in cancer therapies because ROS and specific proteases are overproduced in cancer cells. Methionine-based polypeptides containing a thioether group are promising candidates due to their ROS-responsiveness which provides a phase transition. Herein, we developed protease-activatable cell-penetrating peptide containing a ROS-responsive methionine, a cell permeable lysine chain, and a matrix metalloproteinase (MMP)-cleavable linker. We designed a poly(L-methionine-block-L-lysine)-PLGLAG-PEG (MLMP) and doxorubicin (DOX) was loaded into the micelle core. The MLMP exhibited MMP-sensitive cleavage and ROS-induced DOX release. Moreover, we confirmed efficient DOX delivery into cancer cells and induction of the apoptotic capability in vitro. In a bio-distribution study, IR-780 dye encapsulated MLMP showed superior tumor targetability with long retention. Furthermore, MLMP (DOX) exhibited outstanding tumor inhibition capability with non-toxicity compared to free DOX, indicating that dual stimuli-MLMP has great potential as an anticancer drug delivery platform.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2017-10
Language
English
Article Type
Article
Keywords

GENE DELIVERY; OXIDATIVE STRESS; IN-VIVO; INTRACELLULAR DELIVERY; PCL NANOPARTICLES; EFFICIENT; MICELLES; CONJUGATE; PLATFORM; RELEASE

Citation

JOURNAL OF CONTROLLED RELEASE, v.264, pp.89 - 101

ISSN
0168-3659
DOI
10.1016/j.jconrel.2017.08.026
URI
http://hdl.handle.net/10203/226704
Appears in Collection
BS-Journal Papers(저널논문)CBE-Journal Papers(저널논문)
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