Abstract
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are recognized as one of the most promising agents for theranostic applications. Among methods designed for siRNA delivery, magnetofection, that is, nucleic acid cell uptake under the influence of a magnetic field acting on magnetic nucleic acid vectors, is emerging as a unique approach to combining advantages such as strong improvement of the kinetics of the delivery process and the possibility of localizing nucleic acid delivery to an area where the magnetic field is applied. This paper reports on the preparation of siRNA loaded magnetoplexes—named ICD@SS@SPIONs/siRNA—by controlled crosslinking, in the presence of SPIONs, of the polycation INU-C-DETA, synthesized starting from the polysaccharide inulin by grafting diethylenetriamine and cystamine molecules. The obtained ICD@SS@SPIONs/siRNA have suitable chemical-physical characteristics to be employed for iv administration and are also able to release siRNA in a redox-triggered manner thanks to intracellular glutathione (GSH) mediated reduction of disulphide bridges formed during the crosslinking process. Moreover, ICD@SS@SPIONs/siRNA are able to produce magnetic targeting in vitro on breast cancer cells, without appreciable cyto- and hemo-toxic effects, in a wide range of concentrations. Finally, protein binding to nanoparticles revealed that obtained systems are potentially longer circulating and applicable as a smart multifunctional agents for cancer therapy.
Highlights
Small interfering RNA duplexes are oligonucleotides composed of usually 20–25 base pairs in length that can regulate silencing of the target genes by triggering sequence-specific mRNA degradation [1]
When the experiment was repeated with the Results show how after 24 h, free Small interfering RNA (siRNA) exposed to the RNase showed a 29.83% increase in
These data demonstrate that the incorporation of siRNA inside ICD@SS@SPIONs effectively protected it of some extent against degradation
Summary
Small interfering RNA (siRNA) duplexes are oligonucleotides composed of usually 20–25 base pairs in length that can regulate silencing of the target genes by triggering sequence-specific mRNA degradation [1]. The use of siRNA mediated gene silencing has recently emerged as a promising therapeutic strategy for the treatment of various diseases including cancer, by down-regulating the expression of relevant target genes in a precise and specific manner [2,3]. Despite their high therapeutic potential, siRNAs suffer from degradation by ubiquitous RNase and their high molecular weight, hydrophilicity and negative charge prevent them to adequately penetrate cell membranes [4]. Magnetofection is a recent method designed for nucleic acid based drugs delivery, full of promising advantages such as: (1) potential to increase the response to the administered nucleic acid
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