Structural exploration of hydrophobic core in polycationic micelles for improving siRNA delivery efficiency and cell viability

2019 ◽  
Vol 7 (6) ◽  
pp. 965-973 ◽  
Author(s):  
Wenjun Huang ◽  
Xiaoxia Wang ◽  
Changrong Wang ◽  
Lili Du ◽  
Jianhua Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Sirna Delivery ◽  
Hydrophobic Core ◽  
Delivery Efficiency

Improving siRNA delivery efficiency often encounters a dilemma with poor or decreased biocompatibility for polycationic micelles.

Effects of hydrophobic core components in amphiphilic PDMAEMA nanoparticles on siRNA delivery

Biomaterials ◽  
2015 ◽  
Vol 48 ◽  
pp. 45-55 ◽  
Author(s):  
Shangcong Han ◽  
Qiang Cheng ◽  
Yidi Wu ◽  
Junhui Zhou ◽  
Xingwen Long ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Hydrophobic Core ◽  
Core Components

scholarly journals Pioneering siRNA-Mediated Protection of Mammalian Cells against Zika Virus (MR-766) Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 45
Author(s):  
Benedita K. L. Feron ◽  
Joachim J. Bugert ◽  
Simon C. W. Richardson
Keyword(s):  
Cell Viability ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Sirna Delivery ◽  
Lethal Factor ◽  
Firefly Luciferase ◽  
Delivery Systems ◽  
Zikv Infection ◽  
Huh7 Cells

Here, we present empirical data documenting the siRNA-mediated protection of cells after Zika virus (ZIKV) infection. siRNAs were designed to target well-conserved sequences across the ZIKV genome. Several delivery technologies were utilized. After the electroporation of 100 nM siRNA into human hepatocyte-derived carcinoma (Huh7) cells, the Feron Zv-2 sequence (specific to the ZIKV NS3 gene) yielded a cell viability of 150.3% ± 7.4% (SEM: n = 4) (p = 0.0004) relative to the cells treated only with the virus (33.9% ± 12%, SEM: n = 4). Furthermore, 100 nM siRNA Feron Zv-4 (specific to ZIKV 3’UTR) resulted in 119.1% ± 11.2% cell viability (SEM: n = 4) relative to the control cells treated with ZIKV (p = 0.0021). The cells were electroporated with siRNA prior to ZIKV infection and viability was monitored four days after this. Additionally, two novel siRNA delivery systems were tested. The first utilized recombinant Bacillus anthracis PA83 (octomer-forming mutants), co-incubated with the N-terminal 255 amino acids of B. anthracis lethal factor (LFn) fused in-frame with the RNA binding domain for human protein kinase R (LFn-PKR) at a concentration of 50 µg/mL (each). Here, baby hamster kidney (BHK) cells, treated with 100 nM siRNA Feron Zv-1, yielded 79.0% ± 4.0% viability relative to the control (50.2% ± 1.7%, SEM: n = 3) three days after exposure to ZIKV (p = 0.0096). Finally, HeLa exosomes loaded with siRNA Feron-Zv2 were incubated with Huh7 cells prior to ZIKV infection. For the siRNA-exosome treated cells, a viability of 123% ± 46% (SEM: n = 18), relative to 8% ± 16% (SEM: n = 18) for the same concentration of control HeLa exosomes, was recorded (p = 0.0416). In each instance, 0.3 moI was used and cell viability monitored using the PierceTM Firefly Luciferase Glow Assay Kit by Thermo ScientificTM. Here, we show for the first time that siRNA can significantly reduce ZIKV-induced cell killing. Future work will require quantitating ZIKV mRNA in relation to siRNA treatment, as well as testing the siRNAs and delivery systems within more complex models.

Precision delivery of RAS-inhibiting siRNA to pancreatic cancer via peptide-based nanoparticles.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 287-287 ◽  
Author(s):  
Matthew S. Strand ◽  
Hua Pan ◽  
Bradley Krasnick ◽  
Xiuli Zhang ◽  
Peter S. Goedegebuure ◽  
...  
Keyword(s):  
Cell Death ◽  
Fluorescence Microscopy ◽  
Cell Viability ◽  
Imaging System ◽  
Sirna Delivery ◽  
Ph Sensing ◽  
Stromal Component ◽  
Cancer Types

287 Background: Greater than 95% of pancreatic adenocarcinomas (PDACs) are driven by KRAS activation; yet, despite decades of work, no RAS inhibitors have reached the clinic. Furthermore, the delivery of therapeutic agents of any kind to PDAC has been hindered by the extensive desmoplasia that accompanies these tumors. Herein, we show that serum-stable and pH-sensing nanoparticles (NPs) are taken up by PDAC cells, can deliver KRAS-specific siRNA into the cytoplasm and inhibit KRAS expression, thereby causing cell death. We go on to use a spontaneous model of pancreas cancer to show that this system can effectively deliver siRNA to stroma-rich tumors. Methods: The murine PDAC cell line KP1 was tested for NP uptake in vitro utilizing fluorescent siRNA NPs (fNPs) in combination with confocal microscopy and flow cytometry. KP1 cells were treated with KRAS-siRNA NP, and KRAS expression and cell viability were assessed with RT-PCR and CellTiter-Glo, respectively. Mice bearing subcutaneous KP1 tumors and KPPC mice with spontaneous PDAC were injected with fNP, and tumor fluorescence was assessed using an in vivo imaging system and fluorescence microscopy. Results: KP1 cells take up fNP in vitro, with > 99% of cells positive for fluorescent signal at 24 hours. Treatment with KRAS-siRNA NP of KP1 cells reduced KRAS expression by 69% (see Figure) and reduced cell viability by 45% compared to untreated and scramble-siRNA treated controls. Gemcitabine demonstrated an additive effect with anti-KRAS therapy. Tumors from KP1 cells grown in mice, and tumors from KPPC mice, were strongly fluorescent 24 hours after IV injection of fNP. Fluorescence microscopy showed successful delivery of fNP to tumors. Conclusions: Our NP system can precisely deliver siRNA to KP1 cells and spontaneous PDAC, overcoming the predominant stromal component in these tumors. KRAS-siRNA delivery downregulates KRAS expression, leading to cell death. This represents a novel treatment for PDAC. Furthermore, with its ability to deliver siRNA into the tumor microenvironment and suppress a known oncogene, this platform could be used to target other putative drivers of tumor progression across various cancer types.

scholarly journals Efficient in vivo siRNA delivery by stabilized d-peptide-based lipid nanoparticles

RSC Advances ◽  
2017 ◽  
Vol 7 (15) ◽  
pp. 8823-8831 ◽  
Author(s):  
Tsogzolmaa Ganbold ◽  
Gerile Gerile ◽  
Hai Xiao ◽  
Huricha Baigude
Keyword(s):  
Sirna Delivery ◽  
Lipid Nanoparticles ◽  
Tissue Targeting ◽  
Delivery Efficiency

A lipid functionalized d-dipeptide has shown remarkable biocompatibility and tissue targeting as well as excellent RNAi delivery efficiency in vivo.

scholarly journals Dendrimers as Carriers for siRNA Delivery and Gene Silencing: A Review

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Jiangyu Wu ◽  
Weizhe Huang ◽  
Ziying He
Keyword(s):  
Gene Silencing ◽  
Delivery System ◽  
Sirna Delivery ◽  
Dna Delivery ◽  
Small Interfering Rnas ◽  
Dna And Rna ◽  
Promising Tool ◽  
Knowing That ◽  
Delivery Efficiency ◽  
Sirna Delivery System

RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.

Alkylation enhances biocompatibility and siRNA delivery efficiency of cationic curdlan nanoparticles

2020 ◽  
Vol 143 ◽  
pp. 118-125 ◽  
Author(s):  
Tseyenkhorloo Erdene-Ochir ◽  
Tsogzolmaa Ganbold ◽  
Jargalmaa Zandan ◽  
Shuqin Han ◽  
Gereltu Borjihan ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Delivery Efficiency

scholarly journals Improved siRNA delivery efficiency via solvent-induced condensation of micellar nanoparticles

2017 ◽  
Vol 28 (20) ◽  
pp. 204002 ◽  
Author(s):  
Juan Wu ◽  
Wei Qu ◽  
John-Michael Williford ◽  
Yong Ren ◽  
Xuesong Jiang ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Delivery Efficiency ◽  
Micellar Nanoparticles

Conjugated polymer dots for biocompatible siRNA delivery

2019 ◽  
Vol 43 (36) ◽  
pp. 14443-14449 ◽  
Author(s):  
Fei Wang ◽  
Haobin Chen ◽  
Zhihe Liu ◽  
Feixue Mi ◽  
Xiaofeng Fang ◽  
...  
Keyword(s):  
Conjugated Polymer ◽  
Sirna Delivery ◽  
Fluorescence Properties ◽  
Polymer Dots ◽  
Delivery Efficiency

The constructed nanoplatform not only retained the outstanding fluorescence properties and biocompatibility but also enhanced delivery efficiency of siRNA.

scholarly journals Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing

TECHNOLOGY ◽  
2016 ◽  
Vol 04 (01) ◽  
pp. 42-54 ◽  
Author(s):  
Daniel Vocelle ◽  
Olivia M. Chesniak ◽  
Amanda P. Malefyt ◽  
Georgina Comiskey ◽  
Kwasi Adu-Berchie ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Sirna Delivery ◽  
Scavenger Receptor ◽  
Cell Types ◽  
Delivery Vehicle ◽  
Highly Active ◽  
Independent Process ◽  
Delivery Vehicles ◽  
Interfering Rna ◽  
Delivery Efficiency

Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.

Sign in / Sign up

Export Citation Format

Share Document