title: Reduction-sensitive, robust vesicles with a non-covalently modifiable surface as a multifunctional drug-delivery platform.
abstract: The design and synthesis of a novel reduction-sensitive, robust, and biocompatible vesicle (SSCB[6]VC) are reported, which is self-assembled from an amphiphilic cucurbit[6]uril (CB[6]) derivative that contains disulfide bonds between hexaethylene glycol units and a CB[6] core. The remarkable features of SSCB[6]VC include: 1) facile, non-destructive, non-covalent, and modular surface modification using exceptionally strong host-guest chemistry; 2) high structural stability; 3) facile internalization into targeted cells by receptor-mediated endocytosis, and 4) efficient triggered release of entrapped drugs in a reducing environment such as cytoplasm. Furthermore, a significantly increased cytotoxicity of the anticancer drug doxorubicin to cancer cells is demonstrated using doxorubicin-loaded SSCB[6]VC, the surface of which is decorated with functional moieties such as a folate-spermidine conjugate and fluorescein isothiocyanate-spermidine conjugate as targeting ligand and fluorescence imaging probe, respectively. SSCB[6]VC with such unique features can be used as a highly versatile multifunctional platform for targeted drug delivery, which may find useful applications in cancer therapy. This novel strategy based on supramolecular chemistry and the unique properties of CB[6] can be extended to design smart multifunctional materials for biomedical applications including gene delivery.
authors.affiliation: National Creative Research Initiative Center for Smart Supramolecules (CSS) Department of Chemistry and Division of Advanced Materials Science Pohang University of Science and Technology (POSTECH) Pohang 790-784, Republic of Korea.
authors.forename: Kyeng Min
authors.initials: KM
authors.lastname: Park
authors.forename: Don-Wook
authors.initials: DW
authors.lastname: Lee
authors.forename: Bijay
authors.initials: B
authors.lastname: Sarkar
authors.forename: Hyuntae
authors.initials: H
authors.lastname: Jung
authors.forename: Jeeyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Ko
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.forename: Kimoon
authors.initials: K
authors.lastname: Kim
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010084:Oxidation-Reduction / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013095:Spermidine / Q000737:chemistry; D013499:Surface Properties; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D008024:Ligands; D053835:Unilamellar Liposomes; D004317:Doxorubicin; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate; D013095:Spermidine