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

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

Antisense oligonucleotides for the arterial hypertension mechanisms study and therapy

Arterial hypertension is one of the most common chronic diseases in adults all over the world. This pathology can not only reduce patients’ life quality, but can also be accompanied by a number of complications. Despite the fact that there is a large group of antihypertensive drugs on the market, mainly representing different combinations of inhibitors of the renin-angiotensin system, adrenoreceptor blockers in combination with diuretics, there is no generally accepted “gold standard” for drugs that would not have side effects. The review discusses the main aspects of antisense oligonucleotides use in the context of arterial hypertension. It is well known that the medical implementation of antisense oligonucleotides aims to block the expression of particular genes involved in the pathology development, and a key advantage of this technique is a high selectivity of the effect. However, with the undoubted advantages of the method, there are difficulties in its application, related both to the properties of the oligonucleotides themselves (insufficient stability and poor penetration into cells), and to the variety of mechanisms of the origin of a particular pathology, arterial hypertension, in our case. The review provides a brief description of the main molecular targets for antisense treatment of hypertensive disease. The newest targets for therapy with oligonucleotides – microRNAs – are discussed. The main modifications of antisense nucleotides, designed to increase the duration of their effects and simplify the delivery of this type of drugs to the targets are discussed, in particular, combining antisense oligonucleotides with adenovirus-based expression vectors. Particular attention is given to antisense oligonucleotides in the complex with nanoparticles. The review discusses the results of the use of titanium dioxide (TiO2) containing antisense nanocomposites for the angiotensin converting enzyme in rats with stress induced arterial hypertension (ISIAH). It was shown that the use of antisense oligonucleotides continues to be a promising technique for studying the mechanisms of various forms of hypertensive disease and has a high potential for therapeutic use