期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 21, 期 44, 页码 15651-15666出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201501966
关键词
dendrimers; gene transfection; mesoporous materials; nanoparticles; non-viral vectors
资金
- Ministerio de Economia y Competitividad (MINECO) [MAT2012-35556, CSO2010-11384-E]
- MINECO [CTQ2011-23245]
- UAH [CCG2013/EXP032]
- CAM (Consortium NANODENDMED) [S2011/BMD-2351]
- Ministerio de Educacion
- VI National RDi Plan
- Iniciativa Ingenio
- Consolider Program
- Instituto de Salud Carlos III
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.
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