REDV–polyethyleneimine complexes for selectively enhancing gene delivery in endothelial cells

Yang, Jing; Li, Wen; Lv, Juan; Feng, Yakai; Ren, Xiang‐Kui; Zhang, Wencheng

doi:10.1039/c6tb00686h

Cited by 27 publications

(26 citation statements)

References 53 publications

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“…Thus, the positive charge of these peptides decreased when H n sequence increased from 4 to 12. According to the cytotoxicity assay, the relative cell viability of the peptides and their gene complexes was higher than 80% even at a high concentration (120 μg mL −1 ), which showed a brilliant low cytotoxicity compared with PEI (25 kDa) [ 66 ]. The cellular uptake and MFI of the complexes increased when the H n sequence length increased from 4 to 12.…”

Section: Discussionmentioning

confidence: 99%

Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing cellular uptake and promoting angiogenesis in vivo

Hao

Zaidi

et al. 2018

J Nanobiotechnol

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BackgroundGene therapy has been developed and used in medical treatment for many years, especially for the enhancement of endothelialization and angiogenesis. But slow endosomal escape rate is still one of the major barriers to successful gene delivery. In order to evaluate whether introducing oligohistidine (Hn) sequence into gene carriers can promote endosomal escape and gene transfection or not, we designed and synthesized Arg-Glu-Asp-Val (REDV) peptide functionalized TAT-NLS-Hn (TAT: typical cell-penetrating peptide, NLS: nuclear localization signals, Hn: oligohistidine sequence, n: 4, 8 and 12) peptides with different Hn sequence lengths. pEGFP-ZNF580 (pZNF580) was condensed by these peptides to form gene complexes, which were used to transfect human umbilical vein endothelial cells (HUVECs).ResultsMTT assay showed that the gene complexes exhibited low cytotoxicity for HUVECs. The results of cellular uptake and co-localization ratio demonstrated that the gene complexes prepared from TAT-NLS-Hn with long Hn sequence (n = 12) benefited for high internalization efficiency of pZNF580. In addition, the results of western blot analysis and PCR assay of REDV-TAT-NLS-H12/pZNF580 complexes showed significantly enhanced gene expression at protein and mRNA level. Wound healing assay and transwell migration assay also confirmed the improved proliferation and migration ability of the transfected HUVECs by these complexes. Furthermore, the in vitro and in vivo angiogenesis assay illustrated that these complexes could promote the tube formation ability of HUVECs.ConclusionThe above results indicated that the delivery efficiency of pZNF580 and its expression could be enhanced by introducing Hn sequence into gene carriers. The Hn sequence in REDV-TAT-NLS-Hn is beneficial for high gene transfection. These REDV and Hn functionalized TAT-NLS peptides are promising gene carriers in gene therapy.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0358-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing cellular uptake and promoting angiogenesis in vivo

Hao

Zaidi

et al. 2018

J Nanobiotechnol

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“…According to the previous work described, we carried out this experiment with little modification . Briefly, the L929 mouse fibroblast cells were seeded on 96‐well plates at a density of approximately 2 × 10 4 cells per well in 200 μL culture medium and incubated overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Genipin crosslinked microspheres as an effective hemostatic agent

Xiao

et al. 2018

Polymers for Advanced Techs

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Efficient hemorrhage control is of extreme importance to decrease mortality rates arising from traumatic bleeding. However, traditional hemostatic agents are limited to unsatisfied biocompatibility, inconvenient usage, and high cost. To this end, we have devised a novel hemostatic microsphere from chitosan and gelatin by using appropriate amount of genipin as a crosslinker. The performance of these Cs/GelMPs was evaluated with experiments in vitro and in vivo. Results in vitro showed that the best hemostatic efficacy was achieved by Cs/Gel-0.75 MPs (the mass fraction of genipin in Cs/Gel mixture is 8.6 × 10 −6 ). Skin laceration model indicated that the hemostatic time of Cs/Gel-0.75 MPs was within 12 seconds, which has been significantly shortened in comparison with commercial available products. Moreover, cytocompatibility results displayed that Cs/Gel-0.75 MPs caused no obvious cytotoxicity even at the high concentration of 40 μg/ml. Cs/Gel-0.75 MPs also possess satisfactory fluid absorption ratio and low hemolysis. Therefore, these Cs/Gel-0.75 MPs are promising candidates for further surgical wound hemostatic agent.

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“…Various studies have proved the advantages and potential application of pZNF580 in the transfection of ECs 17,23 . Different cationic polymers have been used to carry pZNF580 to ECs 16,21,23‐31 . These cationic polymers can form positive charge complexes (polyplexes) with DNA due to the electrostatic interaction between the positively charged polymers and negatively charged DNA.…”

Section: Introductionmentioning

confidence: 99%

Bioreducible cationic random copolymer for gene delivery

Muhammad

Zhou

Ullah

et al. 2020

Polymers for Advanced Techs

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Cationic polymers have been widely investigated for gene delivery, although their low transfection efficiency and high cytotoxicity limit their application. We synthesized a bioreducible cationic random copolymer, poly(cystamine bisacylamide‐aminoethyl piperazine)‐co‐poly(cystamine bisacylamide‐histamine) (denoted as CBA‐AEP‐His) from N,N′‐cystamine bis acrylamide (CBA) with aminoethyl piperazine (AEP) and histamine (His). CBA‐AEP‐His copolymer possesses disulfide linkages that endow it with redox‐responsivity to the intracellular environment. This polymer efficiently condenses pZNF580 into complexes with the size of 160 ± 4 nm to 280 ± 5 nm and positive zeta potential of 20 ± 0.3 mV to 30 ± 0.4 mV. The gel‐retardation assay shows that CBA‐AEP‐His can retard pZNF580 even at a low mass ratio of 1/1. The gene complexes were triggered to release pZNF580 when exposed to the reducing environment of dithiothreitol (DTT). CBA‐AEP‐His random copolymer presented higher buffer capacity owing to its His moieties, which protected pZNF580 from DNase degradation. The gene transfection results reveal that CBA‐AEP‐His can efficiently deliver pZNF580 and transfect EA. Hy926 cells. The MTT assay indicates that CBA‐AEP‐His and its complexes exhibit lower cytotoxicity than PEI25KDa. These results illustrate that CBA‐AEP‐His had promising properties for gene delivery, which may provide a suitable platform for the development of a non‐viral gene carrier.

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REDV–polyethyleneimine complexes for selectively enhancing gene delivery in endothelial cells

Abstract: Gene therapy provides a new strategy for promoting endothelialization, and rapid endothelialization has attracted increasing attention for inhibiting thrombosis and restenosis in artificial vascular implants.

Cited by 27 publications

References 53 publications

Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing cellular uptake and promoting angiogenesis in vivo

Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing cellular uptake and promoting angiogenesis in vivo

Genipin crosslinked microspheres as an effective hemostatic agent

Bioreducible cationic random copolymer for gene delivery

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