Abstract
There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation.
Highlights
Despite great efforts, vast resources and impressive progress in medicine and biology in recent years, scientists still have failed to find effective drugs for the treatment of people suffering from leukemia, and there is a constant search for new and improved pharmaceuticals for this disease.Gene therapy has received significant attention due to its potential use in replacement of abnormal genes and treatment of so far incurable diseases [1,2]
In the present work we describe the properties of complexes formed by phosphorus dendrimers of generation 3 and 4 with siRNAs directed against the BCR gene responsible for the development of chronic myeloid leukemia
Since naked nucleic acids or oligodeoxynucleotides (ODNs) are poorly transported into cells by endocytosis [21,22], a delivery system is required for antisense activity in cell culture
Summary
Vast resources and impressive progress in medicine and biology in recent years, scientists still have failed to find effective drugs for the treatment of people suffering from leukemia, and there is a constant search for new and improved pharmaceuticals for this disease. Gene therapy has received significant attention due to its potential use in replacement of abnormal genes and treatment of so far incurable diseases [1,2]. Small interfering siRNAs (siRNA) are a new class of drugs for cancer. These small molecules mediate a process called RNA interference, in which expression of a homologous gene is silenced or inhibited [3].
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