Journal
BIOMATERIALS
Volume 103, Issue -, Pages 56-66Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.06.044
Keywords
Diselenide bond; Polymeric micelle; In situ crosslinking; ROS-responsive release; Biostability; Drug delivery
Funding
- Korea Healthcare Technology R&D Project of MHW [HI14C03810200]
- National R&D Program for Cancer Control of MHW [1420040]
- Basic Science Research Programs of NRF [20100027955, 2015R1A2A2A05001390]
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Stimuli-responsive micelles have emerged as the drug carrier for cancer therapy since they can exclusively release the drug via their structural changes in response to the specific stimuli of the target site. Herein, we developed the in situ diselenide-crosslinked micelles (DCMs), which are responsive to the abnormal ROS levels of tumoral region, as anticancer drug carriers. The DCMs were spontaneously derived from selenol-bearing triblock copolymers consisting of polyethylene glycol (PEG) and poly peptide derivatives. During micelle formation, doxorubicine (DOX) was effectively encapsulated in the hydrophobic core, and diselenide crosslinks were formed in the shell. The DCMs maintained their structural integrity, at least for 6 days in physiological conditions, even in the presence of destabilizing agents. However, ROS-rich conditions triggered rapid release of DOX from the DOX-encapsulating DCMs (DOX-DCMs) because the hydrophobic diselenide bond was cleaved into hydrophilic selenic acid derivatives. Interestingly, after their systemic administration into the tumor-bearing mice, DOX-DCMs delivered significantly more drug to tumors (1.69-fold and 3.73-fold higher amount compared with their non-crosslinked counterparts and free drug, respectively) and effectively suppressed tumor growth. Overall, our data indicate that DCMs have great potential as drug carriers for anticancer therapy. (C) 2016 Elsevier Ltd. All rights reserved.
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