Fluorination effect to intermediate molecular weight polyethylenimine for gene delivery systems

Lee, Gyeong Jin; Kim, Tae-Il

doi:10.1002/jbm.a.36753

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…High cytotoxicity represents an obstacle for practical use of PEI when used as a delivery carrier both in vitro and in vivo . Our previous study reported that modification with perfluorinated groups alone had no major effect on the cytotoxicity of PEI, while another study with PEI-Ch copolymers showed decreased toxicity when compared with the parent PEI . We measured cytotoxicity of the copolymers and PEI in B16F10 cells.…”

Section: Resultsmentioning

confidence: 99%

“…27 Our previous study reported that modification with perfluorinated groups alone had no major effect on the cytotoxicity of PEI, 12 while another study with PEI-Ch copolymers showed decreased toxicity when compared with the parent PEI. 28 We measured cytotoxicity of the copolymers and PEI in B16F10 cells. The cell viability curves and calculated IC 50 values of all the polymers are summarized in Figure 4 and Table S2.…”

Section: ■ Introductionmentioning

confidence: 99%

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Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery

Luo

et al. 2020

Bioconjugate Chem.

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Polyethylenimine (PEI) is a promising delivery vector of nucleic acids, but cytotoxicity and only moderate transfection efficacy with small RNAs limit its applications. Here we hypothesized that hydrophobization of PEI by combined modification with perfluorinated moieties (F) and cholesterol (Ch) will help in addressing both the cytotoxicity and siRNA delivery efficacy. To test the hypothesis, we synthesized a series of copolymers (F-PEI-Ch) by modifying PEI by reaction with heptafluorobutyric anhydride and cholesteryl chloroformate. We investigated and compared the effect of the modifications on siRNA delivery in vitro and in vivo. We found that the F-PEI-Ch copolymers assembled into micellar structures and that the copolymer with the highest Ch content exhibited the best siRNA delivery performance, including lower cytotoxicity, enhanced cell uptake, improved endosomal escape, and the best siRNA silencing efficacy in vitro and in vivo when compared with control PEI, F-PEI, and PEI-Ch. Overall, hydrophobization of PEI with a combination of cholesterol and superhydrophobic perfluorinated moieties represents a promising approach to the design of siRNA delivery vectors with decreased toxicity and enhanced transfection efficacy.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery

Luo

et al. 2020

Bioconjugate Chem.

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“…The fluorination of PEI chains was demonstrated to be an efficient strategy to provide enhanced serum stability and cellular uptake, although the degree of substitution has to be precisely controlled to balance cytotoxicity and intracellular delivery issues. [146] In the same framework, the modification of PEI with cholesterol (Chol) along with superhydrophobic perfluorinated (F) moieties (F-PEI-Chol) evidenced to provide enhanced stability, cellular uptake and siRNA silencing, as well as lower cytotoxicity compared to PEI, F-PEI and PEI-Chol. [147] The hydrophobic modification of low molar mass PEI by using short propionic acid (PrA) has been also hypothesized to enhance transfection efficiency.…”

Section: Hydrophobization Of Pei Chainsmentioning

confidence: 99%

Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine

Oliveira

Albuquerque

Delecourt

et al. 2021

CGT

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Background: Gene delivery is a promising technology for treating diseases linked to abnormal gene expression. Since nucleic acids are the therapeutic entities in such approach, a transfecting vector is required because the macromolecules are not able to efficiently enter the cells by themselves. Viral vectors have been evidenced to be highly effective in this context; however, they suffer from fundamental drawbacks, such as the ability to stimulate immune responses. The development of synthetic vectors has accordingly emerged as an alternative. Objectives: Gene delivery by using non-viral vectors is a multi-step process that poses many challenges, either regarding the extracellular or intracellular media. We explore the delivery pathway and afterwards, we review the main classes of non-viral gene delivery vectors. We further focus on the progresses concerning polyethylenimine-based polymer-nucleic acid polyplexes, which have emerged as one of the most efficient systems for delivering genetic material inside the cells. Discussion: The complexity of the whole transfection pathway, along with a lack of fundamental understanding, particularly regarding the intracellular trafficking of nucleic acids complexed to non-viral vectors, probably justifies the current (beginning of 2021) limited number of formulations that have progressed to clinical trials. Truly, successful medical developments still require a lot of basic research. Conclusion: Advances in macromolecular chemistry and high-resolution imaging techniques will be useful to understand fundamental aspects towards further optimizations and future applications. More investigations concerning the dynamics, thermodynamics and structural parameters of polyplexes would be valuable since they can be connected to the different levels of transfection efficiency hitherto evidenced.

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“…Studies by Vierling, , Chen, and others , have shown that fluorination of gene vectors by incorporation of fluorocarbon chains into the vector molecules is an effective strategy to enhance their antiserum ability, improve the gene complex stability, and lower the cytotoxicity. The fluorocarbon chains are chemically and biologically inert and feature both hydrophobicity and lipophobicity, which can lead to a high tendency toward phase separation in polar and apolar environments .…”

Section: Introductionmentioning

confidence: 99%

A NIR Aggregation-Induced Emission Fluoroamphiphile as Visually Trackable and Serum-Tolerant Nonviral Gene Carrier

et al. 2022

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Functional fluorescence (FL) nonviral gene vectors with high serum tolerance bear broad application prospects in gene delivery. Fluorination has been widely utilized as an effective strategy to enhance serum tolerance. Herein, we show the combination of fluorination and aggregation-induced emission (AIE) for the construction of a nonviral gene vector with low cytotoxicity, visual tracking ability, and high serum tolerance. Large π-conjugation triphenylamine (TPA) derivative with a characteristic D−π−A structure was modified with two polar [12]aneN 3 heads and a long fluorocarbon tail, giving the vector molecule FluoTPA. FluoTPA features near-infrared (NIR) emission, large Stokes shift, and strong binding affinity toward nucleic acids. Liposomes consisting of FluoTPA and dioleoylphosphatidylethanolamine (DOPE) (FluoTPA/DOPE) can effectively deliver both plasmid DNAs (pDNAs) and siRNAs into cells. Impressively, FluoTPA/DOPE showed comparable transfection efficiency (TE) in the presence of serum content up to 30% with that in the serum-free condition and achieved 7.4 times higher TE than the commercial transfection agent lipofectamine 2000 at the same condition. Finally, spatiotemporal tracking of the delivery process in cells was demonstrated. The results in this work suggest that FluoTPA could be a reliable theranostic platform for the nonviral delivery of nucleic acid therapeutics in serum condition.

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Fluorination effect to intermediate molecular weight polyethylenimine for gene delivery systems

Cited by 5 publications

References 51 publications

Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery

Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery

Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine

A NIR Aggregation-Induced Emission Fluoroamphiphile as Visually Trackable and Serum-Tolerant Nonviral Gene Carrier

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