scholarly journals In Vitro Cellular Uptake and Transfection of Oligoarginine-Conjugated Glycol Chitosan/siRNA Nanoparticles

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4219
Author(s):  
Eun-Ju Jeong ◽  
Jangwook Lee ◽  
Hyun-Seung Kim ◽  
Kuen-Yong Lee
Keyword(s):  
Transfection Efficiency ◽  
Physicochemical Characteristics ◽  
Gene Carrier ◽  
Glycol Chitosan ◽  
Arginine Residues ◽  
Low Toxicity ◽  
Low Cytotoxicity ◽  
Low Solubility ◽  
Positively Charged

Chitosan and its derivatives have been extensively utilized in gene delivery applications because of their low toxicity and positively charged characteristics. However, their low solubility under physiological conditions often limits their application. Glycol chitosan (GC) is a derivative of chitosan that exhibits excellent solubility in physiological buffer solutions. However, it lacks the positive characteristics of a gene carrier. Thus, we hypothesized that the introduction of oligoarginine peptide to GC could improve the formation of complexes with siRNA, resulting in enhanced uptake by cells and increased transfection efficiency in vitro. A peptide with nine arginine residues and 10 glycine units (R9G10) was successfully conjugated to GC, which was confirmed by infrared spectroscopy, 1H NMR spectroscopy, and elemental analysis. The physicochemical characteristics of R9G10-GC/siRNA complexes were also investigated. The size and surface charge of the R9G10-GC/siRNA nanoparticles depended on the amount of R9G10 coupled to the GC. In addition, the R9G10-GC/siRNA nanoparticles showed improved uptake in HeLa cells and enhanced in vitro transfection efficiency while maintaining low cytotoxicity determined by the MTT assay. Oligoarginine-modified glycol chitosan may be useful as a potential gene carrier in many therapeutic applications.

Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter

2016 ◽  
Vol 4 (12) ◽  
pp. 2208-2218 ◽  
Author(s):  
Young-Dong Kim ◽  
Tae-Eun Park ◽  
Bijay Singh ◽  
Kye-Soo Cho ◽  
Jaiprakash N. Sangshetti ◽  
...  
Keyword(s):  
Liver Cell ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Gene Carrier ◽  
Cell Targeting ◽  
Cellular Regulation ◽  
Efficient Gene ◽  
Low Cytotoxicity

A new polylactitol-based multifunctional gene carrier has shown low cytotoxicity, a high transfection efficiency, and liver cell targeting bothin vitroandin vivo.

scholarly journals Ar-23 Derivatives With High Endosomal Disrupting Ability Enhance Poly(L-lysine)-mediated Gene Transfection

2020 ◽  
Author(s):  
Shikun Zhang ◽  
Lin Gong ◽  
Xue Zhang ◽  
Zhi-min Yun ◽  
Su-Bo Li ◽  
...  
Keyword(s):  
Transfection Efficiency ◽  
Gene Transfection ◽  
Physicochemical Characteristics ◽  
Cationic Polymer ◽  
Ph Sensitive ◽  
Lytic Activity ◽  
Endosomal Escape ◽  
Charged Residues ◽  
Low Cytotoxicity ◽  
Positively Charged

Abstract Background：pH-sensitive peptides are a relatively new strategy for conquering poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides (AMPs) by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improved its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection.Methods：In the present study, we investigate the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 for enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in AR-23's sequence with Glu one-by-one. The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking，the transfection efficiency, and the cytotoxicity of the polyplexes were determined.Results：Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in AR-23's sequence greatly improved PLL-mediated gene transfection efficiency while maintaining low cytotoxicity.Conclusion：The results indicate that replacement of positively-charged residues with enough Glu residues may be considered a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

Bio-inspired gene carriers with low cytotoxicity constructed via the assembly of dextran nanogels and nano-coacervates

Nanomedicine ◽  
2020 ◽  
Vol 15 (13) ◽  
pp. 1285-1296 ◽  
Author(s):  
Chenglong Wang ◽  
Jiayi You ◽  
Miaomiao Gao ◽  
Peipei Zhang ◽  
Guoxiong Xu ◽  
...  
Keyword(s):  
Positive Charge ◽  
Transfection Efficiency ◽  
Gene Carrier ◽  
Gene Carriers ◽  
Environmentally Responsive ◽  
Potential Applications ◽  
Internal Peptide ◽  
The Common ◽  
Low Cytotoxicity ◽  
Peptide Gene

Aim: To achieve safe and biocompatible gene carriers. Materials & methods: A core/shell-structured hierarchical carrier with an internal peptide/gene coacervate ‘core’ and a dextran nanogel ‘shell’ on the surface has been designed. Results: The dextran nanogels shield coacervate (DNSC) can effectively condense genes and release them in reducing environments. The dextran nanogel-based ‘shell’ can effectively shield the positive charge of the peptide/gene coacervate ‘core’, thus reducing the side effects of cationic gene carriers. In contrast with the common nonviral gene carriers that had high cytotoxicities, the DNSC showed a high transfection efficiency while maintaining a low cytotoxicity. Conclusion: The DNSC provides an effective environmentally responsive gene carrier with potential applications in the fields of gene therapy and gene carrier development.

scholarly journals Immunomodulatory Action of Triterpene Glycosides Isolated from the Sea Cucumber Actinocucumis typica. Structure-Activity Relationships

2014 ◽  
Vol 9 (6) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Evgeny A. Pislyagin ◽  
Dmitry L. Aminin ◽  
Alexandra S. Silchenko ◽  
Sergey A. Avilov ◽  
Pelageya V. Andryjashchenko ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Triterpene Glycosides ◽  
Cytotoxic Activities ◽  
Ros Formation ◽  
Low Toxicity ◽  
Low Cytotoxicity ◽  
Immunomodulatory Action ◽  
Mouse Peritoneal Macrophages ◽  
Stimulation Of

Stimulation of lysosomal activity and ROS formation in mouse peritoneal macrophages by five triterpene glycosides, typicosides A1 (1), A2 (2), B1 (3), C1 (4) and C2 (5) has been studied and compared with their cytotoxic activities. Glycosides 1–3 possess moderate activities, but the most cytotoxic glycoside 5 is not active. Typicoside C1 (4), with low toxicity, was proved to be the most active concerning stimulation of ROS formation. This is the first example of a triterpene glycoside from sea cucumbers with low cytotoxicity, but which demonstrates a strong immunostimulatory effect on mouse peritoneal macrophages in vitro.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

scholarly journals The Development of Functional Non-Viral Vectors for Gene Delivery

2019 ◽  
Vol 20 (21) ◽  
pp. 5491 ◽  
Author(s):  
Patil ◽  
Gao ◽  
Lin ◽  
Li ◽  
Dang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
High Efficiency ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Gene Vectors ◽  
Potential Applications ◽  
Low Toxicity ◽  
Low Cytotoxicity

Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

Defined pH-sensitive nanogels as gene delivery platform for siRNA mediated in vitro gene silencing

2017 ◽  
Vol 5 (11) ◽  
pp. 2328-2336 ◽  
Author(s):  
Mathias Dimde ◽  
Falko Neumann ◽  
Felix Reisbeck ◽  
Svenja Ehrmann ◽  
Jose Luis Cuellar-Camacho ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gene Silencing ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Ph Sensitive ◽  
Carrier System ◽  
High Transfection Efficiency ◽  
Delivery Platform ◽  
Low Cytotoxicity

An advanced cationic carrier system which combines high transfection efficiency with low cytotoxicity and a control over the release of the encapsulated genetic material by the reduction of the multivalent architecture upon pH triggered degradation was developed.

NOVEL POLYETHYLENIMINE NANOGELS AS POTENTIAL GENE CARRIERS PRODUCED VIA PHOTOCHEMISTRY IN SURFACTANT-FREE AQUEOUS SOLUTION

2006 ◽  
Vol 05 (06) ◽  
pp. 753-756 ◽  
Author(s):  
DONGMEI XU ◽  
JIAHUI YU ◽  
YONGBIAO LIU ◽  
HANWEN SUN ◽  
JINGYING XU ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Transfection Efficiency ◽  
In Vitro Tests ◽  
Gene Carriers ◽  
Polymeric Particles ◽  
Potential Applications ◽  
Novel Method ◽  
Low Toxicity

Cationic polymer nanogels, positively-charged submicrometer polymeric particles that swell in water, have attracted an increasing research attentions in recent years because of their potential applications as gene carriers. In this paper, we report a novel method to synthesize polyethylenimine (PEI) nanogels with sizes ranging from 80 nm to 200 nm via UV irradiation at room temperature in aqueous solution without adding any kind of surfactants. The morphology of the nanoparticles is determined to be spherical. The nanogels are of high stability, high transfection efficiency, low toxicity and low immunogenicity, as having been confirmed by in vivo tests with mice as an animal model, and by in vitro tests with human lung and liver cancer cells as well.

α,β-Poly(l-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency

2009 ◽  
Vol 5 (7) ◽  
pp. 2485-2494 ◽  
Author(s):  
Jia-Hui Yu ◽  
Ji-Shan Quan ◽  
Jin Huang ◽  
Cheng-Yun Wang ◽  
Bo Sun ◽  
...  
Keyword(s):  
Transfection Efficiency ◽  
Gene Carrier ◽  
High Transfection Efficiency ◽  
Low Toxicity

scholarly journals DEVELOPMENT OF MUCOADHESIVE CHITOSAN-BASED DRUG DELIVERY SYSTEM

2018 ◽  
Vol XXIII ◽  
pp. 103-113
Author(s):  
Mariya Konovalova ◽  
Balzhima Shagdarova ◽  
Anastasia Zubareva ◽  
Alexander Generalov ◽  
Maria Grechikhina ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Small Intestine ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Mucous Membranes ◽  
Colon Cell ◽  
Reactive Groups ◽  
Low Toxicity ◽  
Positively Charged

Chitosan is a highly versatile biopolymer characterised by low toxicity, biocompatibility, and slow but complete biodegradation in the human body, possessing multiple reactive groups. One of the most well-known properties of positively charged chitosan derivatives is their ability to bind mucous membranes. The aim of this work was the analysis of mucoadhesion of unmodified 20 kDa chitosan and its hydrophobic (HC) and hydrophobic quaternised (QHC) derivatives in vitro and ex vivo. Unmodified chitosan formed large aggregates in vitro in keratinocyte and colon cell cultures and ex vivo in murine small intestine and muscle explants. At the same time, HC and especially QHC bound cells in vitro and ex vivo in a fine dotted manner, as evidenced by confocal microscopy. Such a pattern of hydrophobic derivatives distribution provides the possibility to develop mucoadhesive drug delivery systems with increased local drug release and improved chitosan biodegradation.

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