Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non‐viral Oligonucleotide Delivery Carriers

Abstract

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on their external surface is reported. This system is able to transport single oligonucleotide strands into cells, avoiding the electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating in physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the nanoparticles outer surface. As nucleic acid model, a single stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalized with the third generation of neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro using a human osteoblast-like cell line, achieving good levels of internalization of the vector DNA/carbosilane dendron functionalized material without affecting cellular viability.

Gold nanoparticles stabilized by cationic carbosilane dendrons: synthesis and biological properties

“…Since this framework is highly hydrophobic, the presence of cationic moieties on the periphery of them helps also to make them water soluble. With this aim, a platform of cationic carbosilane dendrons with different focal points were designed and different materials were functionalized, such as poly(D, L-lactide-co-glycolide) acid (PLGA) nanoparticles, 31 mesoporous silica, 32 4 or also were decorated with a fluorescent label. 30 In the view of these attractive properties of carbosilane dendrimers, we have investigated the way to translate them to other macromolecular systems.…”

Dendritic Mesoporous Silica Nanoparticles for pH‐Stimuli‐Responsive Drug Delivery of TNF‐Alpha

“…X‐ray scattering measurements showed the amorphous character of the DMSN and confirmed the pore sizes measured by N 2 ‐sorption (Figures S4 and S5, Supporting Information). 29 Si solid‐state nuclear magnetic resonance spectra (ssNMR) showed a low degree of crosslinking in the silica network and successful dye labeling of DMSN (Figure S6, Supporting Information). Colloidal stability of DMSN‐F was evaluated in phosphate‐buffered saline (PBS) buffer (150 × 10 −3 m , pH 7.3) and ethylenediaminetetraacetic acid (EDTA) plasma before and after functionalization with the pH‐sensitive gatekeeper by dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS) (Figure B,C and Figure S7 and Table S2, Supporting Information).…”

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

“…For example in a contribution from Vallet-Regí and co-workers, the functionalization of MSNs with carbosilane dendrimeric branches allowed to graft a perfectly known number of permanent cations. 148 For this study, the authors took advantage of the high molecular weight of the dendrimeric branches, which allowed the precise estimation of branches incorporated throughout systematic thermogravimetric measures; furthermore their narrow weight distribution allowed the development of unprecedented hybrid material with great possibilities for transfection and gene therapy. Another novel application reported peptide functionalized MSNs, although out of the scope of the present revision, is the size separation of DNA fragments, 149 which relies on the variable electrostatic interaction between DNA strands and polylysine chains.…”