Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles

Khalvati, Bahman; Sheikhsaran, Fatemeh; Sharifzadeh, Sedigheh; Kalantari, Tahereh; Behzad-Behbahani, Abbas; Jamshidzadeh, Akram; Dehshahri, Ali

doi:10.1080/21691401.2016.1202256

Cited by 31 publications

(32 citation statements)

References 39 publications

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“…35,36 However, some controversial studies on the impact of vector unpackaging in elevated transfection efficiency have been reported. 33,[35][36][37] In other words, the polymers with lower plasmid condensation ability will not necessarily lead to higher transfection efficiencies. According to several studies on the impact of polymer binding strength on gene delivery, it seems that facilitating the carrier dissociation is not a promising approach to promote gene transfer ability unless it is considered as the rate-limiting step in the process of gene transfer into the cells.…”

Section: Binding Affinity Of Pei Derivative To Pdnamentioning

confidence: 99%

Targeted double domain nanoplex based on galactosylated polyethylenimine enhanced the delivery of IL‐12 plasmid

Dehshahri

Sadeghpour

Mohazzabieh

et al. 2020

Biotechnology Progress

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The objective of the present investigation was to design a targeted polyethylenimine (PEI)-based polyplex by conjugating lactose bearing galactose groups on low molecular weight PEI (LMW PEI) grafted to a high molecular weight PEI (HMW PEI) via a succinic acid linker in order to restore the amine content of the whole conjugate used for ligand conjugation. The PEI conjugate was synthesized and characterized in terms of buffering capacity, particle size, zeta potential, plasmid condensation ability, and protection of DNA against degrading enzymes. Also, the transfection efficiency and cytotoxicity were evaluated in the cell line over-expressing asialoglycoprotein receptors (ASGPRs) and compared with the cells lacking the receptors. The results demonstrated the ability of PEI conjugate in condensation of plasmid DNA and protection against enzyme degradation. The PEI conjugate formed nanoparticles of around 75 nm with higher buffering capacity compared with unmodified PEI. The polyplexes prepared by the modified PEI could increase the level of transgene up to four folds in the cells over-expressing the receptor. The results demonstrated the separation of targeting and delivery domains could be considered as a strategy to restore the amine content of the PEI molecule utilized for targeting ligand conjugation.

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Section: Binding Affinity Of Pei Derivative To Pdnamentioning

confidence: 99%

Targeted double domain nanoplex based on galactosylated polyethylenimine enhanced the delivery of IL‐12 plasmid

Dehshahri

Sadeghpour

Mohazzabieh

et al. 2020

Biotechnology Progress

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“…12 Reduction of buffering capacity following the hydrophobic modification of various PEI molecules has been reported in several previous investigations. 13,[19][20][21][22][23]25 This decrease is highly associated with the conjugation strategies used for the grafting of various moieties on PEI structure.…”

Section: Biophysical Properties Of Pei Conjugates and The Polyplexes mentioning

confidence: 99%

“…[14][15][16] Hence, several chemical modifications as well as conjugation of PEI with various chemical moieties have been examined in order to decrease the toxic effects of PEI. 13,[17][18][19][20][21][22][23][24][25] Since high molecular weight PEI induces more toxicity, there are several reports suggesting the application of low molecular weight PEI (LMW PEI) as the core of the transfection vector and modifying it to increase its transfection efficiency. 15,[26][27][28][29][30][31][32] Considering the effect of hydrophobic modification of PEI in increasing the transfection efficiency, we hypothesized that cross-linking LMW PEIs using potentially biodegradable linkages such as amides enhances its gene transfer ability with minimal toxic effects.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

Nouri¹,

Sadeghpour²,

Heidari³

et al. 2017

IJN

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Various strategies have been utilized to improve both gene transfer efficiency and cell-induced toxicity of polyethylenimine (PEI), the most extensively investigated cationic polymeric vector. In this study, we sought to enhance transfection efficiency of low molecular weight PEI (LMW PEI) while maintaining its low toxicity by cross-linking LMW PEI via succinic acid linker. These modifications were designed to improve the hydrophilic–hydrophobic balance of the polymer, by enhancing the buffering capacity and maintaining low cytotoxic effects of the final conjugate. Decreased expression of CD200 in the central nervous system has been considered as one of the proposed mechanisms associated with neuroinflammation in multiple sclerosis; therefore, we selected plasmid-encoding CD200 gene for transfection using the modified PEI derivatives. Dynamic light scattering experiments demonstrated that the modified PEIs were able to condense plasmid DNA and form polyplexes with a size of approximately 130 nm. The highest level of CD200 expression was achieved at a carrier to plasmid ratio of 8, where the expression level was increased by 1.5 fold in the SH-SY5Y cell line, an in vitro model of neurodegenerative disorders. Furthermore, the results of in vivo imaging of the LMW PEI-based nanoparticles in the mouse model of multiple sclerosis revealed that fluorescently labeled plasmid encoding CD200 was distributed from the injection site to various tissues and organs including lymph nodes, liver, brain, and finally, kidneys. The nanoparticles also showed the ability to cross the blood–brain barrier and enter the periventricular area.

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“…The obtained results suggested that introduction of the ligand into the side chains of the polymer will allow the receptor-mediated cell-specific and enhanced gene transfection. PEI-based nanoparticles conjugated to succinic anhydride have been reported previously for delivery of interleukin 12 gene into hepatocytes (Khalvati et al 2016). The results revealed that the conjugated PEI derivatives enhanced the transfection efficiency by up to three-fold in comparison to unmodified PEI.…”

Section: Introductionmentioning

confidence: 74%

Hydrophobically modified polyethylenimine-based ternary complexes for targeting brain tumor: stability, in vitro and in vivo studies

Dube

Pandey

Joshi

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Hydrophobic modification of low molecular weight polyethylenimine (PEI 2 kDa) by cholic acid (ChA) was done to obtain PEI2-ChA. The nanoplexes of PEI2-ChA with gWIZ-GFP demonstrated increase transfection efficiency (∼27%) in NT8e cell lines. The cell-cycle analysis of NT8e cells (p53 mutant) treated with transferrin containing nanoplexes showed increased apoptosis of cells. In vitro protein expression revealed expression of exogenous p53 protein. In vivo imaging of mice showed localized signal for GFP protein in brain region. The tumors of mice treated with transferrin containing nanoplexes of PEI2-ChA were ∼5 times smaller in size than the tumor of untreated animals.

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Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles

Cited by 31 publications

References 39 publications

Targeted double domain nanoplex based on galactosylated polyethylenimine enhanced the delivery of IL‐12 plasmid

Targeted double domain nanoplex based on galactosylated polyethylenimine enhanced the delivery of IL‐12 plasmid

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

Hydrophobically modified polyethylenimine-based ternary complexes for targeting brain tumor: stability, in vitro and in vivo studies

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