Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA.

Elżbieta Pędziwiatr-Werbicka,Viktar Abashkin,Katarzyna Horodecka,Rafael Gómez,Maria Bryszewska,Javier Sánchez-Nieves,Cornelia E Peña-González,Barbara Klajnert-Maculewicz,F Javier De La Mata,Michał Gorzkiewicz

doi:10.3390/ijms21134647

Abstract

Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl). Using gel electrophoresis, zeta potential and hydrodynamic diameter measurements, as well as transmission electron microscopy, we characterized AgNP:siRNA complexes and demonstrated the stability of nucleic acid in complexes in the presence of RNase. Hemolytic properties of free silver nanoparticles and complexes, their effect on lymphocyte proliferation and cytotoxic activity on HeLa cells were also examined. Confocal microscopy proved the effective cellular uptake of complexes, indicating the possible use of this type of silver nanoparticles as carriers of genetic material in gene therapy.

Highlights

Despite many years of intensive research, no satisfactory anticancer therapy has been developed so far
The first step of the investigation involved the characterization of complexes of dendronized silver nanoparticles (Figure 1, Table 1) and small interfering RNAs (siRNAs)
The ability of AgNPs to form complexes with siRNA as a function of the dendron:siRNA molar ratio was evaluated by electrophoresis in 3%

Summary

Introduction

Despite many years of intensive research, no satisfactory anticancer therapy has been developed so far. Gene therapy is one of the most promising approaches, based on the delivery of therapeutic nucleic acid molecules with different mechanisms of action in cancer cells. One of the proposed methods involves inhibiting or modulating gene expression by introducing small interfering RNAs (siRNAs) that target and neutralize mRNA associated, e.g., with cell proliferation or their response to chemotherapeutic agents [1,2].

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Discussion

Conclusion