Poly-L-lysine Functionalized Large PoreudCubic Mesostructured SilicaudNanoparticles as BiocompatibleudCarriers for Gene Delivery

摘要

Large pore mesoporous silica nanoparticlesud(LP-MSNs) functionalized with poly-udL-lysine (PLL) were designed as a new carrierudmaterial for gene delivery applications. Theudsynthesized LP-MSNs are 100-200 nm in diameterudand are composed of cage-like pores organized in a cubic mesostructure. The size of theudcavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto theudsilica surface through covalent immobilization was confirmed by X-ray photoelectronudspectroscopy, solid-state 13C magic-angle spinning nuclear magnetic resonance, Fourierudtransformed infrared, and thermogravimetric analysis. As a result of the particle modificationudwith PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs wasudobserved compared to the native unmodified silica particles. Consequently, PLL-functionalizedudnanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Helaudcells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as geneudcarriers compared to amino-functionalized nanoparticles and the native nanoparticles. Theudsystem was tested to deliver functional siRNA against minibrain-related kinase and polo-likeudkinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated greatudpotential for efficient gene transfer into cancer cells as a decrease of the cellular viability of theudosteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles alsoudexhibit a high biocompatibility, with low cytotoxicity observed up to 100 μg/mL.