ABSTRACT

The cellular internalization of oligonucleotide-modified nanoparticles is investigated. Uptake is dependent on the density of the oligonucleotide loading on the surface of the particles, where higher densities lead to greater uptake. The introduction and development of the oligonucleotide–nanoparticle conjugate have led to applications in molecular diagnostics, materials synthesis, and gene regulation. In the case of therapeutic applications, the use of oligonucleotides for genetic regulation holds promise for both the investigation of gene function and the treatment of disease, and thus developing new agents to both effectively deliver and utilize oligonucleotides in cellular systems is important. A hallmark of these densely functionalized oligonucleotide- modified particles is their ability to enter a wide variety of cell types, which has qualitatively been demonstrated using confocal microscopy. Quantification of the cellular uptake of these mixed monolayer particles demonstrated that uptake is highly dependent on the number of oligonucleotides immobilized on each antisense oligonucleotide-modified gold nanoparticle agents.