Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection

Alexander S Timin,Kirill V Lepik,Maria V Okilova,Boris V Afanasyev,Gleb B Sukhorukov,Andrey V Vasin,Aleksandra V Petrova,Albert R Muslimov

doi:10.1038/s41598-017-00200-0

Abstract

The implementation of RNAi technology into the clinical practice has been significantly postponing due to the issues regarding to the delivery of naked siRNA predominantly to target cells. Here we report the approach to enhance the efficiency of siRNA delivery by encapsulating the siRNA into new carrier systems which are obtained via the combination of widely used layer-by-layer technique and in situ modification by sol-gel chemistry. We used three types of siRNAs (NP-717, NP-1155 and NP-1496) in encapsulated form as new therapeutic agents against H1N1 influenza virus infection. By employing the hybrid microcontainers for the siRNA encapsulation we demonstrate the reduction of viral nucleoprotein (NP) level and inhibition of influenza virus production in infected cell lines (MDCK and A549). The obtained hybrid carriers based on assembled biodegradable polyelectrolytes and sol-gel coating possess several advantages such as a high cell uptake efficiency, low toxicity, efficient intracellular delivery of siRNAs and the protection of siRNAs from premature degradation before reaching the target cells. These findings underpin a great potential of versatile microencapsulation technology for the development of anti-viral RNAi delivery systems against influenza virus infection.

Highlights

At the moment, four licensed influenza antiviral prescription drugs can be used for treatment or prevention of influenza[4]
We examine the potency of novel microcontainers for delivery of antiviral short interfering RNAs (siRNAs)
We further study the morphology and shell thickness of our hybrid capsules using transmission electron microscopy (TEM)

Summary

Introduction

Four licensed influenza antiviral prescription drugs can be used for treatment or prevention of influenza[4]. Among the diversity of carriers, polyelectrolyte (PE) microcapsules prepared by the layer-by-layer (LbL) technique had been demonstrated as an unique tool for in situ encapsulation of the genetic materials to perform highly efficient in vitro delivery[25,26,27,28,29,30]. These capsules have many attributes that lend to their application in biomedicine. The use of SiO2 can enhance the bioactive behavior of modified materials, due to the possibility to be internalized into cells and SiO2 can be dissolved in biological environments[42]

Methods

Results

Conclusion