Poly(l-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides

Silica nanoparticles were prepared in a microemulsion system, using polyoxyethylene nonylphenyl ether/cyclohexane/ammonium hydroxide. The surface charge of the particle was modified with PLL [poly(l‐lysine)]. PAGE demonstrated the ability of PMS‐NP (PLL‐modified silica nanoparticles) to bind and protect antisense ODNs (oligonucleotides). The intracellular localization of FITC‐labelled ODN was investigated by fluorescence microscopy. The results demonstrated that ODN could be delivered to cytoplasm. Flow‐cytometry analysis showed a 20‐fold enhancement of ODN delivered by PMS‐NP compared with free ODN for a serum‐free medium. Blocking efficacy of c‐myc antisense ODN, delivered by PMS‐NP, was examined in HNE1 and HeLa cell lines. Significant down‐regulation of c‐myc mRNA levels was observed in both the cell lines. However, the cellular uptake efficiency and antisense effects on target gene decreased in the presence of serum‐containing medium. The analysis of the filtration assay showed that PMS‐NP interacted with serum proteins. These results indicated that PMS‐NP was a suitable delivery vector for antisense ODN, although its delivery efficiency decreased in the presence of a serum‐containing medium.