Engineering cellular degradation of multilayered capsules through controlled cross-linking

Kang Liang, Georgina Kate Such, Zhiyuan Zhu, Sarah J Dodds, Angus Johnston, Jiwei Cui, Hirotaka Ejima, Frank Caruso

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)10186 - 10194
Number of pages9
JournalACS Nano
Volume6
Issue number11
DOIs
Publication statusPublished - 2012
Externally publishedYes

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