scholarly journals Cationic liposome–nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing

2016 ◽  
Vol 374 (2072) ◽  
pp. 20150129 ◽  
Author(s):  
Ramsey N. Majzoub ◽  
Kai K. Ewert ◽  
Cyrus R. Safinya
Keyword(s):  
Nucleic Acid ◽  
Gene Delivery ◽  
Gene Silencing ◽  
Liquid Crystalline ◽  
Cationic Liposome ◽  
Endosomal Escape ◽  
Cubic Phase ◽  
Nucleic Acid Therapeutics

Cationic liposomes (CLs) are synthetic carriers of nucleic acids in gene delivery and gene silencing therapeutics. The introduction will describe the structures of distinct liquid crystalline phases of CL–nucleic acid complexes, which were revealed in earlier synchrotron small-angle X-ray scattering experiments. When mixed with plasmid DNA, CLs containing lipids with distinct shapes spontaneously undergo topological transitions into self-assembled lamellar, inverse hexagonal, and hexagonal CL–DNA phases. CLs containing cubic phase lipids are observed to readily mix with short interfering RNA (siRNA) molecules creating double gyroid CL–siRNA phases for gene silencing. Custom synthesis of multivalent lipids and a range of novel polyethylene glycol (PEG)-lipids with attached targeting ligands and hydrolysable moieties have led to functionalized equilibrium nanoparticles (NPs) optimized for cell targeting, uptake or endosomal escape. Very recent experiments are described with surface-functionalized PEGylated CL–DNA NPs, including fluorescence microscopy colocalization with members of the Rab family of GTPases, which directly reveal interactions with cell membranes and NP pathways. In vitro optimization of CL–DNA and CL–siRNA NPs with relevant primary cancer cells is expected to impact nucleic acid therapeutics in vivo . This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.

scholarly journals Cationic liposome–nucleic acid complexes for gene delivery and gene silencing

2014 ◽  
Vol 38 (11) ◽  
pp. 5164-5172 ◽  
Author(s):  
Cyrus R. Safinya ◽  
Kai K. Ewert ◽  
Ramsey N. Majzoub ◽  
Cecília Leal
Keyword(s):  
Nucleic Acid ◽  
Gene Delivery ◽  
Gene Silencing ◽  
Cationic Liposome

Cationic Liposome-DNA Complexes: Polymorphism versus Transfection Activity

2000 ◽  
Vol 6 (S2) ◽  
pp. 854-855
Author(s):  
B. Sternberg-Papahadjopoulos ◽  
K. Hong ◽  
W. Zheng ◽  
D. Papahadjopoulos
Keyword(s):  
Electron Microscopy ◽  
Cultured Cells ◽  
Freeze Fracture ◽  
Cationic Liposome ◽  
Specific Structure ◽  
Spherical Particles ◽  
Cubic Phase ◽  
Active Structure

Complexes formed during interaction of cationic liposomes with polynucleotides such as DNA (CLDC) self-assemble into a variety of polymorphic structures. They display bilayer (FIG. 1-5) and non-bilayer structures (FIG. 6). We have recorded bilayer structures such as spaghetti/meatball-type structures (FIG. I), map-pins (FIG. 2) spherical particles and invaginated liposomes (FIG. 3, 4) and oligolamellar structures (FIG. 5). The non-bilayer lipid arrangements include honeycombtype structure (Hn, FIG. 6) and cubic phase lipids.We have chosen mainly freeze-fracture electron microscopy (FIG. 1-3, 5,6) but also cryo-electron microscopy (FIG.4) for recording polymorphic structures, and for studying factors and conditions triggering the formation and stabilization of specific structure types. Furthermore, we took microscopically snapshots of the interaction of specific structure types with cultured cells. In order to find out the “active” structure in terms of transfection, we investigated the transfection activity both in vivo and in vitro of CLDC, and studied in parallel their morphology in serum as well as in cell medium.

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

scholarly journals Non-cationic RGD-containing protein carrier for tumor-targeted siRNA delivery

2021 ◽  
Author(s):  
Xiaolin Yu ◽  
Lu Xue ◽  
Jingjing Zhao ◽  
Shuhua Zhao ◽  
Daqing Wu ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Sirna Delivery ◽  
Integrin Αvβ3 ◽  
Cationic Liposome ◽  
Genetically Engineered ◽  
Endosomal Escape ◽  
Widespread Application ◽  
Rgd Peptides

Abstract Despite the recent successes in siRNA therapeutics, targeted delivery beyond the liver remains the major hurdle for the widespread application of siRNA in vivo. Current cationic liposome or polymer-based delivery agents are restricted to the liver and suffer from off-target effect, poor clearance, low serum stability, and high toxicity. In this study, we have genetically engineered a non-cationic tumor-targeted universal siRNA nanocarrier. This protein nanocarrier consists of three function domains: dsRNA binding domain (dsRBD) (from human protein kinase R) for any siRNA binding, 18-histidines for endosome escape, and two RGD peptides at N-and C-termini for targeting tumor and tumor neovasculature. We showed that cloned dual-RGD-dsRBD-18his (dual-RGD) protein protects siRNA against RNases, induces effective siRNA endosomal escape, specific targets on integrin αvβ3 expressing cells in vitro, and homes siRNA to tumor in vivo. The delivered siRNA leads target gene knockdown in the cell lines and tumor xenografts with low toxicity. This multifunctional, biomimetic, charge-neutral siRNA carrier is biodegradable, low toxic, suitable for mass production by fermentation, and serum stable, holding great potential to provide a widely applicable siRNA carrier for tumor-targeted siRNA delivery.

scholarly journals Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

2019 ◽  
Author(s):  
Shubiao Zhang ◽  
Yinan Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in Hela cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplexes was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid.Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo

2009 ◽  
Vol 139 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Hiroto Hatakeyama ◽  
Erika Ito ◽  
Hidetaka Akita ◽  
Motoi Oishi ◽  
Yukio Nagasaki ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Ph Sensitive ◽  
Endosomal Escape

scholarly journals Sugar Functionalized Synergistic Dendrimers for Biocompatible Delivery of Nucleic Acid Therapeutics

Polymers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1034 ◽  
Author(s):  
Shuqin Han ◽  
Tsogzolmaa Ganbold ◽  
Qingming Bao ◽  
Takashi Yoshida ◽  
Huricha Baigude
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Green Fluorescence Protein ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Nucleic Acid Therapeutics ◽  
Fluorescence Protein ◽  
Interfering Rna

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.

scholarly journals Hybrid delivery systems for methotrexate-lipidic liquid crystalline cubic phases and cubosomes with magnetic nanoparticles

2019 ◽  
Author(s):  
Monika Mierzwa ◽  
Pawel Krysinski ◽  
Renata Bilewicz
Keyword(s):  
Magnetic Nanoparticles ◽  
Liquid Crystalline ◽  
Low Frequency ◽  
In Vitro Cytotoxicity ◽  
Cubic Phase ◽  
Hybrid Delivery ◽  
Cubic Phases ◽  
Release Profiles

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

scholarly journals Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

2020 ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the“proton sponge effect”of the lipid. Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

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