کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5433360 | 1508986 | 2017 | 13 صفحه PDF | دانلود رایگان |
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.
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Journal: Journal of Controlled Release - Volume 264, 28 October 2017, Pages 89-101