Peptide-Based Multicomponent Oligonucleotide Delivery Systems: Optimisation of Poly-l-lysine Dendrons for Plasmid DNA Delivery

Kamaruzaman, Khairul Azfar; Moyle, Peter M.; Tóth, István

doi:10.1007/s10989-016-9545-5

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Amino acids play important roles in cell life, acting as cell signaling molecules, regulating gene expression, and synthesizing hormones, among others. These features make them attractive as components of amino acid-based gene carriers for gene therapy, or as a part of different kind of molecules, such as of cationic monovalent or multivalent lipids [1,2,3,4,5,6], polypeptides [7,8,9,10,11], polymers [12,13,14,15], polycations [16] and/or dendrimers [11,17,18,19,20]. Generally, gene therapy has focused on viral and non-viral vectors for the treatment of hereditary or acquired illnesses [21,22,23].…”

Section: Introductionmentioning

confidence: 99%

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

et al. 2018

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This work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C3(C16His)2). Mixed with a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the green fluorescence protein (pEGFP-C3), one encoding a luciferase (pCMV-Luc), and a therapeutic anti-tumoral agent encoding interleukin-12 (pCMV-IL12). Complementary biophysical experiments (zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and fluorescence anisotropy) and biological studies (FACS, luminometry, and cytotoxicity) of these C3(C16His)2/DOPE-pDNA lipoplexes provided vast insight into their outcomes as gene carriers. They were found to efficiently compact and protect pDNA against DNase I degradation by forming nanoaggregates of 120–290 nm in size, which were further characterized as very fluidic lamellar structures based in a sandwich-type phase, with alternating layers of mixed lipids and an aqueous monolayer where the pDNA and counterions are located. The optimum formulations of these nanoaggregates were able to transfect the pDNAs into COS-7 and HeLa cells with high cell viability, comparable or superior to that of the standard Lipo2000*. The vast amount of information collected from the in vitro studies points to this histidine-based lipid nanocarrier as a potentially interesting candidate for future in vivo studies investigating specific gene therapies.

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Section: Introductionmentioning

confidence: 99%

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

et al. 2018

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“…Red fluorescence and green fluorescence located in the nucleus could be observed, indicating that both plasmids and materials could enter into the nucleus. Besides, guanidium groups would also be used to facilitate the escape of DNA into the cytoplasm by interacting with the endosomal membrane; interactions with DNA and cell membranes (Kamaruzaman et al, 2017; Zhu et al, 2011). However, the effect of gene transfection had no close relationship to the amount of the guanidium groups, which supposed to be shielded by the space conformation structure of chitosan molecule.…”

Section: Resultsmentioning

confidence: 99%

“…interactions with DNA and cell membranes (Kamaruzaman et al, 2017;Zhu et al, 2011). However, the effect of gene transfection had no close relationship to the amount of the guanidium groups, which supposed to be shielded by the space conformation structure of chitosan molecule.…”

Section: In Vitro Transfectionmentioning

confidence: 99%

Study on the transfection efficiency of chitosan‐based gene vectors modified with poly‐l‐arginine peptides

Zhang

Chu

Sun

et al. 2020

J Biomedical Materials Res

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Although in a series of studies, arginine peptides had shown the ability to promote the targeting delivery efficacy, the relationship between the transfection efficiency and the length of the poly-l-arginine chain had seldom been reported. This study was aimed to explore whether the chain length of poly-l-arginine grafted on chitosan had a great significance on the transfection efficiency of entering the cells. Herein, arginine and arginine peptide modified chitosan were synthesized as gene vectors (CS-Arg and CS-5Arg) and then the chemical structures were characterized by using 1 H NMR. The CS-Arg and CS-5Arg were combined with plasmids by electrostatic interactions to form stable particles. The morphology features, Zeta potentials, and buffering capacity of the complex particles were analyzed. Afterward, the combination ability with DNA and the protection ability to DNase I were studied, and the gene transfection efficiency and cellular uptake were investigated in vitro. The results showed that the gene transfection efficiency of the chitosan was significantly enhanced by arginine-graft modification. However, there were no significant differences between the CS-Arg and the CS-5Arg. The molecular simulation results indicated that the guanidine groups of grafted arginine were shielded by chitosan molecule and the guanidine groups contributed little to the gene transfection efficiency. The results demonstrated that the increased chain length of grafted arginine had no significantly enhanced effect on the transfection efficiency, which could provide convincing evidence for the construction and application of arginine and chitosan derivatives as gene vectors, and could promote the development of gene delivery system.

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“…This functionalization offers multiple advantages, such as escape from endolysosomal vesicles by the proton sponge effect. Kamaruzaman et al 81 . introduced an oligonucleotide delivery system by functionalization of poly‐ l ‐lysine dendrons with TAT peptide and His residues.…”

Section: Histidine‐modified Peptidesmentioning

confidence: 99%

“…This functionalization offers multiple advantages, such as escape from endolysosomal vesicles by the proton sponge effect. Kamaruzaman et al 81 introduced an oligonucleotide delivery system by functionalization of poly-L-lysine dendrons with TAT peptide and His residues. Moreover, a His-modified-star-shaped polymer carrier with enhanced endosomal escape ability was described by Ren et al 82 Second, the stearyl lipophilic chain enhanced the cellular uptake and endosomal escape ability of resulting peptide by improving the buffering capacity of the His residues.…”

Section: Histidine-modi Fied Peptidesmentioning

confidence: 99%

Histidine‐enhanced gene delivery systems: The state of the art

Hooshmand

Sabet

Hasanzadeh

et al. 2022

The Journal of Gene Medicine

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Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells.The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-L-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.

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Peptide-Based Multicomponent Oligonucleotide Delivery Systems: Optimisation of Poly-l-lysine Dendrons for Plasmid DNA Delivery

Cited by 7 publications

References 39 publications

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

Study on the transfection efficiency of chitosan‐based gene vectors modified with poly‐l‐arginine peptides

Histidine‐enhanced gene delivery systems: The state of the art

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