Niosomes Containing Spermine-Based Cationic Lipid with Different Linkers for siRNA Delivery

2019 ◽  
Vol 819 ◽  
pp. 169-174
Author(s):  
Supusson Pengnam ◽  
Praneet Opanasopit ◽  
Theerasak Rojanarata ◽  
Nattisa Ni-yomtham ◽  
Boon Ek Yingyongnarongkul ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Weight Ratio ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Molar Ratio ◽  
Ionic Surfactant ◽  
Low Toxicity ◽  
Cationic Niosomes

Niosomes are a lipid nanoparticle which have been widely used as non-viral carrier for therapeutic DNA or siRNA. They are formulated from non-ionic surfactant and other helper lipids. The aim of this study were to formulate niosome containing spermine-based cationic lipid with different linkers and to evaluate the efficiency of siRNA delivery in cervical cancer cell (HeLa cell). The niosomes were formulated from cholesterol (Chol), Span 20 and different cationic lipid (Ay, By, Cy and Dy) at various molar ratios. The properties of niosomes and ability of niosome to complex with siRNA were characterized. The cellular uptake, gene silencing efficiency and cytotoxicity were also determined. From the results, niosomes formulated at Chol:Span20:lipid molar ratio of 2.5:2.5:2 showed positive zeta potential and they were in nanosize (<200 nm). The binding ability of cationic niosomes to siRNA depended on types of cationic lipid. Among niosome/siRNA complexes, the niosome By/siRNA complex provided the highest gene silencing efficiency at weight ratio of 20. The highest cellular uptake also obtained by using niosome By as a carrier. The cytotoxicity revealed that cationic niosomes had low toxicity (cell viability > 80%). In conclusion, the cationic niosomes prepared from Chol, Span 20 and spermine-based cationic lipids are able to complex with siRNA and suitable for siRNA delivery with low toxicity.

scholarly journals In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 394 ◽  
Author(s):  
Viktor Maurer ◽  
Selin Altin ◽  
Didem Ag Seleci ◽  
Ajmal Zarinwall ◽  
Bilal Temel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Superparamagnetic Iron Oxide ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Therapy Outcome ◽  
Ionic Surfactant ◽  
Combinational Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

Quaternized starch-based carrier for siRNA delivery: From cellular uptake to gene silencing

2014 ◽  
Vol 185 ◽  
pp. 109-120 ◽  
Author(s):  
Eliz Amar-Lewis ◽  
Aharon Azagury ◽  
Ramesh Chintakunta ◽  
Riki Goldbart ◽  
Tamar Traitel ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Sirna Delivery

PEGylated Plier-Like Cationic Niosomes on Gene Delivery in HeLa Cells

2019 ◽  
Vol 819 ◽  
pp. 151-156
Author(s):  
Supusson Pengnam ◽  
Samarwadee Plianwong ◽  
Kanokwan Singpanna ◽  
Nattisa Ni-yomtham ◽  
Widchaya Radchatawedchakoon ◽  
...  
Keyword(s):  
Particle Size ◽  
Gene Delivery ◽  
Hela Cells ◽  
Transfection Efficiency ◽  
Cationic Lipid ◽  
Dna Delivery ◽  
Molar Ratio ◽  
The Novel ◽  
Low Cytotoxicity ◽  
Cationic Niosomes

Lipid-based formulations have been used as a widespread carrier to improve gene delivery. Niosomes, one type of lipid-based vesicular systems are produced from non-ionic surfactants which are generally inexpensive and potentially more stable than phospholipids. This article was to develop PEGylated cationic niosomes for DNA delivery. Thin film hydration and sonication method were applied for cationic niosomes. The niosome formulations were composed of Span 20, cholesterol (Chol) and plier-like cationic lipid B (PCL-B) with or without cholesterol-polyethylene glycol 2000 (Chol-PEG). The physicochemical properties of cationic niosomes and nioplexes were evaluated including particle size, zeta potential, DNA condensation and serum protection. The transfection efficiency and cell viability were examined in HeLa cells. The particle size and surface charge of PEGylated cationic niosome containing Span 20: Chol: PCL-B: Chol-PEG at the molar ratio of 2.5: 2.5: 1.5: 0.14 (N-PEG2) were 129.47 ± 2.15 nm and 25.93 ± 4.18 mV, respectively. These PEGylated cationic niosomes could condense pDNA into the nanosize particles and also enhance the serum protection ability for at least 6 h. Moreover, N-PEG2 exhibited high transfection efficiency in comparison with lipofectamine® 2000 and low cytotoxicity. Therefore, the novel PEGylated cationic niosomes have the capability to develop as a promising potential carrier for DNA delivery.

scholarly journals Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 89 ◽  
Author(s):  
Emanuela Fabiola Craparo ◽  
Salvatore Emanuele Drago ◽  
Nicolò Mauro ◽  
Gaetano Giammona ◽  
Gennara Cavallaro
Keyword(s):  
Epithelial Cells ◽  
Cellular Uptake ◽  
Intracellular Transport ◽  
Sirna Delivery ◽  
Weight Ratio ◽  
Endosomal Escape ◽  
Bronchial Epithelial ◽  
Vitro Experiment ◽  
In Vitro Experiment

Here, a novel protonable copolymer was realized for the production of polyplexes with a siRNA (inhibitor of STAT6 expression in asthma), with the aim of a pulmonary administration. The polycation was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)d,l-aspartamide (PHEA) with 1,2-Bis(3-aminopropylamino)ethane (bAPAE) in proper conditions to obtain a PHEA-g-bAPAE graft copolymer with a derivatization degree in amine (DDbAPAE%) equal to 35 mol%. The copolymer showed a proper buffering behavior, i.e., ranging between pH 5 and 7.4, to potentially give the endosomal escape of the obtained polycations. In effect, an in vitro experiment demonstrated the effect on biological membranes of the copolymer on bronchial epithelial cells (16-HBE) strongly dependent on the pH of the medium, i.e., higher at pH 5. bAPAE-based copolymers were further obtained with an increasing pegylation degree, i.e., equal to 1.9, 2.7, and 4.4 mol%, respectively. All the obtained copolymers were able to complex siRNA at a N/P ratio that decreases as the pegylation degree increases. At the same time, the tendency of polyplexes to aggregate and the capability to interact with mucin also decreases as the pegylation in the copolymer increases. Gene silencing experiments on 16-HBE showed that these copolymers have a significant role in improving the intracellular transport of naked siRNA, where the presence of PEG does not seem to hinder the cellular uptake of polyplexes. The latter obtained at polymer/siRNA weight ratio (R) equal to 10 with PHEA-g-PEG(C)-g-bAPAE also seems to be not susceptible to the presence of mucin, avoiding the polyanionic exchange of complexed siRNA, thus showing adequate behavior to be used as an effective vector for siRNA.

scholarly journals Novel fusion peptide‐mediated siRNA delivery using self‐assembled nanocomplex

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyung Ah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Immune Cell ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Self Assembled

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

The development of tertiary amine cationic lipids for safe and efficient siRNA delivery

2019 ◽  
Vol 7 (7) ◽  
pp. 2777-2792 ◽  
Author(s):  
Ziming Lin ◽  
Moxyel Bao ◽  
Zexuan Yu ◽  
Lingjing Xue ◽  
Caoyun Ju ◽  
...  
Keyword(s):  
Tertiary Amine ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Cationic Liposomes ◽  
Cationic Lipids

Tertiary amine-derived cationic lipid serves as the primary lipid of cationic liposomes, which can balance the effectiveness and safety of siRNA vectors.

scholarly journals Disulfide-Based Poly(amido amine)s for siRNA Delivery: Effects of Structure on siRNA Complexation, Cellular Uptake, Gene Silencing and Toxicity

2010 ◽  
Vol 28 (5) ◽  
pp. 1013-1022 ◽  
Author(s):  
Pieter Vader ◽  
Leonardus J. van der Aa ◽  
Johan F. J. Engbersen ◽  
Gert Storm ◽  
Raymond M. Schiffelers
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Sirna Delivery

scholarly journals Novel Fusion Peptide-Mediated siRNA Delivery Using Self-Assembled Nanocomplex

2020 ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyungah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang
Keyword(s):  
Gene Therapy ◽  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Self Assembled

Abstract Background: Gene therapy using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine.Results: Among the novel fusion peptides and siRNAs, nanocomplexes have outstanding cellular uptake and gene silencing effect in vitro and high stability and retention effect of siRNAs in vivo. Oligo arginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased stability and retention of siRNAs at the site of the tumor. Conclusions: The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene therapy.

scholarly journals Amylose-Based Cationic Star Polymers for siRNA Delivery

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoki Nishimura ◽  
Kaori Umezaki ◽  
Sada-atsu Mukai ◽  
Shin-ichi Sawada ◽  
Kazunari Akiyoshi
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Star Polymers ◽  
Degree Of Polymerization ◽  
Star Polymer ◽  
Hydrodynamic Diameter ◽  
Polymer Complexes ◽  
Average Hydrodynamic Diameter ◽  
Sirna Delivery System

A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials.

scholarly journals Novel fusion peptide-mediated siRNA delivery using self-assembled nanocomplex

2021 ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyungah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
BYEONG HEE HWANG
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Genetic Level ◽  
Self Assembled

Abstract Background: Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine.Results: Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without immunogenicity.Conclusions: The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

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