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Effective systemic siRNA delivery using dual-layer protected long-circulating nanohydrogel containing inorganic core

Abstract

Systemic delivery of small interfering RNA (siRNA) has been mainly impeded by enzymatic degradation and poor cellular uptake. Calcium phosphate (CaP) has been considered a potential candidate for siRNA delivery because of its excellent biocompatibility and capability of entrapping siRNA in the crystal core. Based on adhesive properties of 3,4-dihydroxy-l-phenylalanine (dopa) to the surface of CaP crystal, dual hydrogel layers consisted of a macromolecular dextran (dex) and polyethylene glycol (PEG) were introduced on the surface of inorganic CaP core for prolonged circulation. Dextran conjugated with dopa and polyethylene glycol (PEG) (PEG-dex-dopa) can effectively control the overgrowth of CaP/siRNA core and stabilize it by dual electrically neutral hydrophilic layers of dextran and PEG, which additionally provide reduced hepatic accumulation and systemic clearance. The dual shield of PEG-dex-dopa nanohydrogel containing CaP/siRNA core (PEG-dex-dopa/CaP/siRNA) significantly improved pharmacokinetic behaviors of siRNA after systemic administration, resulting in the increased distribution to tumor and the effective inhibition of tumor growth by silencing vascular endothelial growth factor (VEGF) gene expression through enhanced permeability and retention (EPR) effect.

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Supplementary files

Publication details

The article was received on 08 Mar 2019, accepted on 03 May 2019 and first published on 10 May 2019


Article type: Paper
DOI: 10.1039/C9BM00369J
Biomater. Sci., 2019, Accepted Manuscript

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    Effective systemic siRNA delivery using dual-layer protected long-circulating nanohydrogel containing inorganic core

    Y. Yin, M. S. Lee, J. E. Lee, S. Y. Lim, E. S. Kim, J. Jung, D. Kim, J. Kim, D. S. Lee and J. H. Jeong, Biomater. Sci., 2019, Accepted Manuscript , DOI: 10.1039/C9BM00369J

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