title: 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.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: V G
authors.initials: VG
authors.lastname: Deepagan
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Seunglee
authors.initials: S
authors.lastname: Kwon
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Van Quy
authors.initials: VQ
authors.lastname: Nguyen
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.
authors.forename: Wooram
authors.initials: W
authors.lastname: Um
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Ko
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Hansang
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea. Electronic address: jhpark1@skku.edu.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000188:drug therapy*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004655:Emulsions; D008823:Micelles; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D004317:Doxorubicin; D012643:Selenium
keywords: Biostability; Diselenide bond; Drug delivery; In situ crosslinking; Polymeric micelle; ROS-responsive release