Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

Abstract

Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@ PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited ( P <0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core–shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs.

An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance

“…The utilisation of polymer-based nanoparticles for enabling the delivery of a spectrum of drugs, including miRNAs, is becoming evermore commonplace with versatile and non-immunogenic polymers such as polyethylenimine and polyethylene glycol being utilised as nanoparticle backbones [121][122][123][124][125]. Typical advantages of the use of polymers for nanoparticle drug delivery systems include a highly flexible drug release kinetic profile on response to acid exposure [93].…”

New Trends for the Processing of Poly(Methyl Methacrylate) Biomaterial for Dental Prosthodontics

“…Several substances such as chitosan [83], PEI (polyethyleneimine) nanoparticles [84], 15% of N-acetyl cysteine (NAC) [87], calcium phosphate cement (CPC) [90], acrylic resin of different colors [91], (bone cement) enriched with microencapsulated 2-octyl cyanoacrylate (OCA), extracts solutions [92], scaffolds fabricated by electrospinning using polycaprolactone (PCL) [94], core/polyethyleneimine (PEI) shell magnetic nanoparticles [97], silver nanoparticles (AgNPs) [98], and Paladon 65-HR precoated with biosurfactant were also evaluated for cytotoxicity. The authors observed reduction in cytotoxicity and increase in biocompatibility from non-cytotoxic (cell viability higher than 75%) to slightly cytotoxic (cell viability ranging from 50 to 75%)…”