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Naji, M. |
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Motta, Antonella |
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Aletan, Dirar |
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Mohamed, Tarek |
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Ertürk, Emre |
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Taccardi, Nicola |
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Petrov, R. H. | Madrid |
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Alshaaer, Mazen | Brussels |
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Bih, L. |
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Casati, R. |
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Kočí, Jan | Prague |
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Kalteremidou, Kalliopi-Artemi | Brussels |
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Azam, Siraj |
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Ospanova, Alyiya |
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Blanpain, Bart |
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Ali, M. A. |
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Popa, V. |
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Rančić, M. |
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Ollier, Nadège |
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Azevedo, Nuno Monteiro |
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Landes, Michael |
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Rignanese, Gian-Marco |
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Dodds, Sarah J.
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article
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.