Abstract
There is an urgent need to develop systems for nucleic acid delivery, especially for the creation of effective therapeutics against various diseases. We have previously shown the feasibility of efficient delivery of small interfering RNA by means of gold nanoparticle-based multilayer nanoconstructs (MLNCs) for suppressing reporter protein synthesis. The present work is aimed at improving the quality of preparations of desired MLNCs, and for this purpose, optimal conditions for their multistep fabrication were found. All steps of this process and MLNC purification were verified using dynamic light scattering, transmission electron microscopy, and UV-Vis spectroscopy. Factors influencing the efficiency of nanocomposite assembly, colloidal stability, and purification quality were identified. These data made it possible to optimize the fabrication of target MLNCs bearing small interfering RNA and to substantially improve end product quality via an increase in its homogeneity and a decrease in the amount of incomplete nanoconstructs. We believe that the proposed approaches and methods will be useful for researchers working with lipid nanoconstructs.
Highlights
Nucleic-acid therapeutics have tremendous therapeutic potential for the treatment of many diseases
The formation of a lipid envelope around the core nanoparticle is mediated by electrostatic interaction between protonated amino groups of the lipid (DOME2, which is a component of the lipid film) and negatively charged phosphate groups of the small interfering RNA (siRNA)
Lipid-coated particles that serve as a carrier of siRNA are the subject of numerous studies
Summary
Nucleic-acid therapeutics have tremendous therapeutic potential for the treatment of many diseases. The number of such therapeutics approved for clinical use is still low [1]. Nucleic acids are very sensitive to nucleases, as evidenced by the low stability of nucleic acids in physiological fluids [3]. These obstacles can be overcome by (i) the development of modifications of nucleic acids and (ii) the creation of delivery systems that ensure penetration into the cell and longer half-life of the nucleic acid formulation in the human body. A distinct field of research and development of these systems is the use of solid (metal) nanoparticles enclosed in a shell and serving as a carrier of a nucleic acid. There are reports on the efficient delivery of small interfering RNA (siRNA) via gold nanoparticles (AuNPs) [9] and selenium nanoparticles [10] coated with chitosan and gold nanorods covered with two layers of polyelectrolytes [11]
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