title: Engineering cellular degradation of multilayered capsules through controlled cross-linking.
abstract: We report a versatile approach for controlling the intracellular degradation of polymer capsules by tailoring the degree of cross-linking in the capsules. Poly(2-diisopropylaminoethyl methacrylate) capsules were assembled by the layer-by-layer technique and covalently stabilized with a redox-responsive bisazide cross-linker using click chemistry. The degree of cross-linking, determined using radiation scintillation counting, was tuned from 65% to 98% by adjusting the amount of cross-linker used to stabilize the polymer films. Transmission electron microscopy and fluorescence microscopy studies showed that the pH responsiveness of the capsules was maintained, regardless of the degree of cross-linking. Atomic force microscopy measurements on planar surfaces revealed that increasing the degree of cross-linking decreased the film roughness (from 8.7 to 1.7 nm), hence forming smoother films; however the film thicknesses were not significantly altered. Cellular studies showed that the rate of intracellular degradation of the capsules could be controlled between 0 and 6 h by altering the degree of cross-linking in the polymer capsules. These studies also demonstrated that the cellular degradation of highly cross-linked capsules (>90%) was significantly retarded compared to degradation in simulated cellular conditions. This suggests that the naturally occurring cellular reducing environment is rapidly depleted, and there is a significant delay before the cells can replenish the reducing environment. The modular and versatile nature of this approach lends itself to application to a wide range of polymer carriers and thus offers significant potential for the design of polymer-based systems for drug and gene delivery.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kang
authors.initials: K
authors.lastname: Liang
authors.forename: Georgina K
authors.initials: GK
authors.lastname: Such
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dodds
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Jiwei
authors.initials: J
authors.lastname: Cui
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ejima
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D003432:Cross-Linking Reagents; D003713:Dendritic Cells / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008422:Materials Testing; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D003432:Cross-Linking Reagents; D053769:Nanocapsules