Effective systemic siRNA delivery using dual-layer protected long-circulating nanohydrogel containing an inorganic core. (12th June 2019)

• Record Type: Journal Article
• Authors: Yin, Yue; Lee, Min Sang; Lee, Jung Eun; Lim, Su Yeon; Kim, E Seul; Jeong, Jaeback; Kim, Dahwun; Kim, Jaeyun; Lee, Doo Sung; Jeong, Ji Hoon
• Is Part Of: Biomaterials science. Volume 7:Number 8(2019)
• Page Start: 3297
• Page End: 3306
• Publication Date: 2019-06-12
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c9bm00369j
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : PEG-dex-dopa nanohydrogel containing a CaP/siRNA core could achieve extended circulation with reduced RES accumulation, resulting in increased tumor accumulation. 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 the property of 3, 4-dihydroxy-l-phenylalanine (dopa) binding to the surface of the CaP crystal, dual hydrogel layers consisting of a macromolecular dextran (dex) and polyethylene glycol (PEG) were introduced on the surface of the inorganic CaP core for prolonged circulation. Dextran conjugated with dopa and polyethylene glycol (PEG) (PEG-dex-dopa) can effectively control the overgrowth of the 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 a CaP/siRNA core (PEG-dex-dopa/CaP/siRNA) significantly improved the pharmacokinetic behaviors of siRNA after systemic administration, resulting in its increased distribution to tumors and the effective inhibition of tumor growth by silencing vascular endothelial growth factor (VEGF) gene expression through the enhanced permeability and retention (EPR) effect.