In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery.

Abstract

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 polypeptide 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.

• Authors: V G Deepagan, Seunglee Kwon, Dong Gil You, Van Quy Nguyen, Wooram Um, Hyewon Ko, Hansang Lee, Dong-Gyu Jo, Young Mo Kang, Jae Hyung Park
• Journal: Biomaterials (Biomaterials) Vol. 103 Pg. 56-66 (10 2016) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 27372421 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Cross-Linking Reagents
• Emulsions
• Micelles
• Nanocapsules
• Reactive Oxygen Species
• Polyethylene Glycols
• Doxorubicin
• Selenium

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry)
• Cell Line, Tumor
• Cross-Linking Reagents (chemistry)
• Doxorubicin (administration & dosage, chemistry)
• Drug Stability
• Emulsions (chemistry)
• Humans
• Male
• Mice
• Mice, Nude
• Micelles
• Molecular Targeted Therapy (methods)
• Nanocapsules (administration & dosage, chemistry, ultrastructure)
• Neoplasms, Experimental (chemistry, drug therapy)
• Particle Size
• Polyethylene Glycols (chemistry)
• Reactive Oxygen Species (chemistry)
• Selenium (chemistry)
• Treatment Outcome