Loading oligonucleotides on a nanoparticle regulated by a grafted polyethylenimine layer

Abstract

Using molecular theory, we systematically investigate the aggregation of oligonucleotides on a polyethylenimine(PEI)-grafted nanoparticle. Here we include the protonation of PEI in the theory, which is basically described as a chemical equilibrium. The key finding of our work is that the maximum loading capacity occurs in the long-chain case, where adsorbed oligonucleotides distribute in multiples layers within the PEI layer due to the meshed structure formed by the grafted long PEI chains. The PEI layer acts as a sponge adsorbing oligonucleotides under the influence of electrostatic attractions between PEI and oligonucleotide. In particular, we address the question of why the complex consisting of the PEI-grafted nanoparticle and adsorbed molecules can be taken up by cells, while the complex has negative surface charge. It is because the electrostatic potential of the complex plays the dominant role. By an analysis of the chemical potential of the PEI layer and free energy of the system, we find that stable complexes are formed during the condensation of the oligonucleotide on the PEI-grafted nanoparticle and the most stable state appears at a specific surface coverage. Finally, the loading capacity is found to greatly depend on the bulk pH. A small change in pH is verified to cause a large variation of the loading capacity. The reason is that the protonation of PEI is very sensitive to the pH value. Our results are important for the understanding of the role of the PEI layer in real applications and may be useful in the design of an optimal drug delivery system.