The Appalication Of Silica Nanoparticles With Special Morphology In Gene Vectors

Silica nanoparticles are attractive candidates for the development of safe and efficient non-viral gene carriers, owing to their controlled morphologies, potential of facile surface modification and excellent biocompatibility as well as in vivo biodegradability. Advanced gene carriers with compromised cytotoxicity could be achieved through lingking low-molecular-weight polycation to silica nanoparticles. In addition, the size and shape of nanoparticles are considered to have an intense influence on their interaction with cells and biological systems, which means that silica-based gene vectors with special morphologies may benefit the gene transfection. In this work, a series of novel gene carriers were designed employing polycation modified silica nanoparticles with different morphologies to investigate the effects of particle size and shape of these different carriers on gene transfection. And then, novel starlike-hollow silica nanoparticles with different sizes were proposed as platforms for the fabrication of redox-triggered multifunctional systems for synergy of gene therapy and chemotherapy. The main work is summarized as follows:1. Polycation functionalized silica nanoparticle (SiO2-g-PDMAEMA) gene carriers was realized employing silica nanoparticles with versatile morphologies as the core and PDMAEMA as grafted brushes via ATRP were designed to investigate the effects of particle sizes and shapes of these carriers on gene transfection. DNA binding capability, cytotoxicity and gene transfection ability of the SiO2-g-PDMAEMA carriers were investigated in detail. Chiral nanorods with larger aspect ratio were found to fabricate the most efficient gene carriers with compromised cytotoxicity. It was also noted that hollow nanosphere-based carriers exhibited better gene transfection performance than solid counterparts. These results may provide new strategies to develop promising gene carriers and useful information for the application of nanoparticles in biomedical areas.2. A novel type of co-delivery carrier of drug and gene (SHNP-PGEA) was successfully fabricated based on intelligent supramolecular gatekeeper-functionalized starlike hollow silica nanoparticles. CD-PGEA could be flexibly introduced onto the surfaces of SHNPs with plentiful disulfide bond-linked Ad guests. The resulting supramolecular assembly (SHNP-PGEA) possessed the intelligent gatekeepers for GSH-induced intracellular drug release. Thus, minimal premature drug escape before reaching the target cancer cells could be realized by the redox-responsive host-guest system. SHNP-PGEA also demonstrates good performances to deliver genes. The DNA binding capability, gene transfection efficiencies, controlled drug release behaviors and synergistic antitumor effect of SHNP-PGEA were investigated in detail. The experiment results show that compared with ordinary spherical HNP-based counterparts, SHNP-PGEA carriers with six sharp horns were proven to be superior gene vectors and possess better efficacy for cellular uptake and antitumor effects. The results show that the present multifunctional carriers based on SHNPs would have promising applications in drug/gene co-delivery and cancer treatment.