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

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.

Impact of Nanocapsules on Red Blood Cells Interplay Jointly Assessed by Optical Tweezers and Microscopy

“…Polymeric nanocapsules (NCs) are a promising system of natural carriers for targeted drug delivery because of their low cytotoxicity, shell flexibility, and high in vivo stability [22][23][24][25][26]. A wide range of drugs [27][28][29] and nucleotides of ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) [30][31][32] can be effectively encapsulated in the polymer capsules. Effective distribution of drugs in target tissues can be achieved by active delivery methods that are potentially much more beneficial than passive accumulation.…”

Current Advances of Hollow Capsules as Controlled Drug Delivery Systems

“…For instance, if the sacrificial templates are made of CaCO 3 or MnCO 3 , polycation polymer like polyethyleneimine (PEI) and poly(allylamine) (PAH) is commonly used to co‐precipitate during their template formation, whereas in terms of silica templates including porous‐ and non‐porous structure, the amine functionalization by 3‐aminopropyltrimethoxysilane is frequently applied . The template functionalization facilitates not only the physical adsorption of therapeutic agents, especially with negatively charged molecules like DNA, siRNA or RNA onto core templates prior to the coating step, but also the deposition of polymeric layers forming capsule walls …”

Cell‐Based Drug Delivery and Use of Nano‐and Microcarriers for Cell Functionalization

“…Many recent studies have investigated the internalization process of LbL polyelectrolyte microcapsules in different cell types . LbL microcapsules have great potential in cell functionalization compared with nanoparticles alone because of the unique properties of LbL microcapsules, such as multiencapsulation capacity and controlled release of low or high molecular weight compounds in response to various external and internal stimuli . LbL capsules can serve as a platform for in situ deposition of various inorganic nanoparticles, resulting in the formation of a composite shell with enhanced physicochemical properties .…”

“…LbL microcapsules have great potential in cell functionalization compared with nanoparticles alone because of the unique properties of LbL microcapsules, such as multiencapsulation capacity and controlled release of low or high molecular weight compounds in response to various external and internal stimuli . LbL capsules can serve as a platform for in situ deposition of various inorganic nanoparticles, resulting in the formation of a composite shell with enhanced physicochemical properties . Such remarkable capsule functions can potentially extend cell properties if such capsules can be internalized .…”