New insights on the mechanism of polyethylenimine transfection and their implications on gene therapy and DNA vaccines

Sabín, Juan; Alatorre-Meda, Manuel; Miñones, J.; Domínguez-Arca, Vicente; Prieto, Gerardo

doi:10.1016/j.colsurfb.2021.112219

Cited by 30 publications

(28 citation statements)

References 72 publications

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“…In addition, confocal microscopy data revealed that PEI enters the cytoplasm, but does not enter the nucleus. 79 As shown in Fig. 3A and B, the cy5 PEI firmly stayed on the cell membrane indicating yellow contours of the cells at the first 2 h. After 6 h incubation, most cy5 PEI still banded on the cytomembrane, and some entered the cytosol and distributed in lysosomes (Fig.…”

Section: Enhanced Cell Uptakementioning

confidence: 75%

Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

et al. 2022

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Section: Enhanced Cell Uptakementioning

confidence: 75%

Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

et al. 2022

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“…A recent study suggested that PEI might influence polyplex intracellular trafficking and participate in the dislocation of therapeutic DNA across the nuclear membrane. The model system demonstrated that bPEI1.8k has the ability to stabilize nuclear membrane nanopores by interactions with the phospholipid bilayer and that it is accompanied by unpacking of polyplex, allowing for the nuclear entry of a therapeutic load [ 21 ]. On the other hand, the grafting of nanosystems with biocompatible hydrophilic polymer chains such as PEO is a common strategy to improve the longevity of nanovehicles under physiological conditions.…”

Section: Resultsmentioning

confidence: 99%

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field

et al. 2022

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Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1–100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

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“…Since the most widely accepted theory of endosomal escape of nucleic acids relies on the ability to attract protons as stated in the proton sponge theory, the DET side chain is a good candidate for nucleic acid delivery into the cell. [40][41][42][43] With both diblock and triblock copolymers, DET proved to be a cationic moiety capable of forming well-defined polyplexes with luc-pDNA leading us to choose it as the optimal cationic block.…”

Section: Discussionmentioning

confidence: 99%

“…The slightly elongated shapes of polyplexes made with mannosylated copolymers could contribute to decreased uptake as Skirtach et al reports that high-aspect ratio particles result in slower and overall decreased uptake compared to spherical particles due to the forces generated at the interaction between cell and particle. [41,44] Therefore, the elongated worm-like shape of mannosylated polyplexes can result in decreased uptake, though there is no clear consensus in the literature. Non-mannosylated triblock AED3-based polyplexes also had both low uptake and poor transfection.…”

Section: Discussionmentioning

confidence: 99%

Poly(2-oxazoline)-based polyplexes as a PEG-free plasmid DNA delivery platform

Yamaleyeva

Makita

Hwang

et al. 2022

Preprint

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The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a PEG-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying non-ionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, we employed azide-alkyne cycloaddition click chemistry methods. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, non-targeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either of these copolymers is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to non-mannosylated polyplexes. Thus, PEG-free, non-targeted DET- and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial non-lipid transfection reagent.

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New insights on the mechanism of polyethylenimine transfection and their implications on gene therapy and DNA vaccines

Cited by 30 publications

References 72 publications

Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field

Poly(2-oxazoline)-based polyplexes as a PEG-free plasmid DNA delivery platform

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