Reduction-sensitive, robust vesicles with a non-covalently modifiable surface as a multifunctional drug-delivery platform.
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.
Park
Kyeng Min
KM
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.
Lee
Don-Wook
DW
Sarkar
Bijay
B
Jung
Hyuntae
H
Kim
Jeeyeon
J
Ko
Young Ho
YH
Lee
Kyung Eun
KE
Jeon
Hyesung
H
Kim
Kimoon
K
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*
D008024:Ligands; D053835:Unilamellar Liposomes; D004317:Doxorubicin; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate; D013095:Spermidine