Abstract
Gold nanoparticles (AuNPs) are a platform for the creation of nanoconstructions that can have a variety of functions, including the delivery of therapeutic nucleic acids. We previously designed a AuNP/small interfering RNA (siRNA) nanoconstruction consisting of siRNA noncovalently bound on the AuNP surface and showed that this construction, when coated with a lipid shell, was an efficient vehicle for the delivery of siRNA into cells. The goal of the present work was to study the possibility of scaling up the synthesis of AuNP-siRNA and its long-term storage without loss of physicochemical characteristics and siRNA duplex integrity as well as siRNA surface density. Dynamic light scattering, transmission electron microscopy, UV–vis spectroscopy, and electrophoresis were used to study the effect of scaling up the AuNP-siRNA synthesis and long term storage of its suspension on physicochemical properties of the samples and integrity of the siRNA duplex. It was shown that a ten-fold increase in the volume of the reaction mixture decreased the surface density of siRNA by about 10%, which influenced the corresponding physicochemical characteristics of the AuNP-siRNA suspension. The storage of the AuNP-siRNA suspension at 4 °C for different times resulted in the formation of particle clusters of high colloidal stability as demonstrated by conventional methods. These clusters completely disintegrated when albumin was added, indicating that they are agglomerates (and not aggregates) of AuNP-siRNA. The AuNPs-siRNA nanoconstruction demonstrated integrity of the siRNA duplex and high stability of the siRNA surface density during storage for seven months at 4 °C. Thus, it can be concluded that it is possible to scale-up the synthesis of noncovalent AuNP-siRNA and to obtain a nanoconstruction possessing high stability in terms of physicochemical characteristics and siRNA surface density for a long period.
Highlights
Drug delivery to cells is only one application of nanoparticles in biomedicine; it occupies an important place in scientific research
Our studies demonstrated that noncovalent binding of Small interfering RNA (siRNA) to the AuNP surface is a promising approach to the creation of theranostic nanoconstructions because this bond maintains siRNA in its physiological form and does not alter the properties and advantages of gold nanoparticles
We studied the second approach since we have previously found that the surface density, which is an important indicator of the quality of the AuNP-siRNA preparations, decreases during concentration [17]
Summary
Drug delivery to cells is only one application of nanoparticles in biomedicine; it occupies an important place in scientific research. Different variants of AuNP-based nanoconstructions bearing siRNA have been published, and most of them were created by applying the layer-by-layer principle [9]. The core of these structures usually consists of a AuNP, where siRNA is covalently bound to the NP surface through the thiol group, and the core is covered with a lipid or polymer shell [10,11,12,13]. Covalent bonding of siRNA to the surface of AuNPs is carried out in two stages: (1) covalent attachment of one chain of a duplex; (2) hybridization of the second chain with the first one. None of the works published to date give information about the cleavage of the covalent bond between siRNA and AuNPs and preservation of the siRNA duplex inside the cell
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