One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA

Autor: Francesco Salvatore, Bruna Corradetti, Seth G. Haddix, Alessandro Parodi, Ennio Tasciotti, Sm Z. Khaled, Shilpa Scaria, Armando Cevenini, Michael Evangelopoulos, Iman K. Yazdi, Claudia Corbo, Ye Hu
Přispěvatelé: Khaled, Sm Z, Cevenini, Armando, Yazdi, Iman K., Parodi, Alessandro, Evangelopoulos, Michael, Corbo, Claudia, Scaria, Shilpa, Hu, Ye, Haddix, Seth G., Corradetti, Bruna, Salvatore, Francesco, Tasciotti, Ennio, Khaled, S, Cevenini, A, Yazdi, I, Parodi, A, Evangelopoulos, M, Corbo, C, Scaria, S, Hu, Y, Haddix, S, Corradetti, B, Salvatore, F, Tasciotti, E
Rok vydání: 2016
Předmět:
Small interfering RNA
Cancer therapy
Polymers
Nanoparticle
02 engineering and technology
01 natural sciences
chemistry.chemical_compound
Organic chemistry
Breast
RNA
Small Interfering
Lysosomal escape
chemistry.chemical_classification
Polymer
Silicon Dioxide
021001 nanoscience & nanotechnology
Mechanics of Materials
Covalent bond
Methacrylates
SiRNA delivery
Female
0210 nano-technology
Nanogel
Receptors
CXCR4
Materials science
Silicon dioxide
Biophysics
Mice
Nude
Breast Neoplasms
Ceramics and Composite
Bioengineering
010402 general chemistry
Article
Biomaterials
Dynamic light scattering
Cations
Cell Line
Tumor
Animals
Humans
Mechanics of Material
PH-responsive polymer
technology
industry
and agriculture
Cationic polymerization
Biomaterial
0104 chemical sciences
RNAi Therapeutics
chemistry
Chemical engineering
Delayed-Action Preparations
Ceramics and Composites
Nanoparticles
Zdroj: Biomaterials. 87:57-68
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2016.01.052
Popis: This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa. Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB-231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression.
Databáze: OpenAIRE
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