Methods of the Synthesis of Silicon-Containing Nanoparticles Intended for Nucleic Acid Delivery

Abstract

A promising new approach to the treatment of viral infections and genetic diseases associated with damaged or foreign nucleic acids in the body is gene therapy, i.e., the use of antisense oligonucleotides, ribozymes, deoxyribozymes, siRNA, plasmid DNA, etc. (therapeutic nucleic acids). Selective recognition of target nucleic acids by these compounds based on highly specific complementary interaction can minimize negative side effects, which occur with currently used low molecular weight drugs. To apply a new generation of therapeutic agents in medical practice, it is necessary to solve the problem of their delivery into cells. Silicon-containing nanoparticles are considered as promising carriers for this purpose due to their biocompatibility, low toxicity, ability to biodegradation and excretion from the body, as well as the simplicity of the synthesis and modification. Silicon-containing nanoparticles are divided into two broad categories: solid (nonporous) and mesoporous silicon nanoparticles (MSN). This review gives a brief overview of the creation of mesoporous, multilayer, and other silicon-based nanoparticles. The publications concerning solid silicon-organic nanoparticles capable of binding and delivering nucleic acids into cells are discussed in more detail with emphasis on methods for their synthesis. The review covers publications over the past 15 years, which describe the classical Stöber method, the microemulsion method, modification of commercial silica nanoparticles, and other strategies.

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

“…Briefly, the reverse microemulsion, or water-in-oil (w/o) system, comprises a homogeneous mixture of water, oil, and surfactant molecules that form reverse micelles. The aqueous phase of the system is then confined to the bulk of the micelles, acting as a nanoreactor for particle formation [ 18 ]. The Stöber method, developed in 1968, is a typical sol–gel process in which a solution gradually evolves towards a gel-like network [ 33 ].…”

“…To complete the process, the surfactant micelles are removed from the silica structure through high-temperature processing (calcination) or by solvent extraction. Using this method, the obtained pore size is usually very uniform and easily tunable by varying the type of surfactant used, but it commonly ranges between 2 and 5 nm [ 8 , 11 , 18 ].…”

“…To complete the process, the surfactant micelles are removed from the silica structure through high-temperature processing (calcination) or by solvent extraction. Using this method, the obtained pore size is usually very uniform and easily tunable by varying the type of surfactant used, but it commonly ranges between 2 and 5 nm [8,11,18]. illustrated in Figure 8, when the silica precursor is added to the solution, it condensates at the surface of the existing micelles, forming a silica structure around them.…”

“…To complete the process, the surfactant micelles are removed from the silica structure through high-temperature processing (calcination) or by solvent extraction. Using this method, the obtained pore size is usually very uniform and easily tunable by varying the type of surfactant used, but it commonly ranges between 2 and 5 nm [8,11,18]. Using cetyltrimethylammonium bromide (CTAB) as a pore template surfactant, Chang and colleagues developed FITC-conjugated MSNs with a hexagonal shape and uniform size of approximately 110 nm, with an average pore size of 2 nm [47].…”

“…The properties of any nanosystem, such as its size or shape, play a major role in its in vivo performance, and therefore, when delivering genetic material, these properties should be carefully tailored in order to enhance the system’s cellular uptake and transfection efficiency. The easily modifiable synthesis of silica-based structures from silane precursors allows the control of these functional properties and even grants the possibility of incorporating different stimuli-responsive organic groups into the silica framework, which can confer the nanosystem with triggered biodegradation properties for the controlled release of payloads [ 18 , 19 ]. Regardless of the system’s core-design and structure, another very important aspect to account for in any silica-based gene delivery system is its surface functionalization [ 20 , 21 ].…”