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

• Published in: Chemistry : a European journal 2015-10, Vol.21 (44), p.15651-15666
• Main Authors: Martínez, Ángel, Fuentes-Paniagua, Elena, Baeza, Alejandro, Sánchez-Nieves, Javier, Cicuéndez, Mónica, Gómez, Rafael, de la Mata, F. Javier, González, Blanca, Vallet-Regí, María
• Format: Article
• Language: English
• Subjects: Chemistry; dendrimers; Dendrimers - chemical synthesis; Dendrimers - chemistry; Deoxyribonucleic acid; DNA; DNA, Single-Stranded - chemistry; Drug Carriers - chemistry; gene transfection; Genetic Vectors - genetics; Grafting; Humans; Ions - chemistry; Magnetic Resonance Spectroscopy; mesoporous materials; Nanoparticles; Nanoparticles - chemistry; non-viral vectors; Nucleic acids; Nucleic Acids - chemistry; Nucleic Acids - metabolism; Oligonucleotides; Oligonucleotides - chemistry; Porosity; Silanes - chemistry; Silicon dioxide; Silicon Dioxide - chemistry; Strategy; Transfection - methods; Vectors (mathematics)
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201501966

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single‐stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under 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 outer surface of the nanoparticles. 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 functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast‐like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron‐functionalised material without affecting the cellular viability. Ready to deliver: Carbosilane dendrons of second and third generation, with ammonium or tertiary amine groups as peripheral groups, have been prepared and different strategies have been used to graft them outside mesoporous silica nanoparticles. The hybrid nanosystem functionalised with the third generation of a neutral carbosilane dendron is able to transport single‐stranded (ss) oligonucleotide into cells, thereby representing a novel non‐viral vector (see figure).