N-Acetyl-<scp>l</scp>-leucine-polyethylenimine-mediated miR-34a delivery improves osteogenesis and bone formationin vitroandin vivo

Shen, Yunzhong; Liu, Zhenying; Gao, Han; Fei, Hongbo; Yu, Wenwen; Hu, Tianqi; Zheng, Yuanyuan; Bi, Xueting; Lin, Chongtao

doi:10.1039/c7ra12548h

Cited by 5 publications

(9 citation statements)

References 31 publications

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“…16 Similarly, N-Ac-L-Leu-PEI leads to better cell viability than PEI25K in RAW264.7 cells. 23,38 The same results were shown in our findings. This may be attributed to the declining cation composition of the complexes and non-specific protein adsorption of N-Ac-L-Leu-PEI, which triggered less cell membrane disruption.…”

Section: Discussionsupporting

confidence: 92%

“…34,35 Therefore, in recent years, macromolecule materials have been used in the delivery of CpG ODN, including graphene oxidechitosan nanocomposites 36 and N-isopropylacrylamidemodified polyethyleneimine (PEN). 37 Previous studies demonstrated that the N-Ac-L-Leu-PEI/CpG ODN 2006 complex (w: w = 1: 1) was superior to microRNAs and single-stranded oligo DNAs (w: w = 2:1) 22,23,38 and to plasmid DNA (w:w = 0.6-0.8:1). 24 The PEN vehicle could completely retard ODN MT01 at a mass ratio of 0.5.…”

Section: Discussionmentioning

confidence: 99%

“…37 Previous studies demonstrated that the N-Ac-L-Leu-PEI/CpG ODN 2006 complex (w: w = 1: 1) was superior to microRNAs and single-stranded oligo DNAs (w: w = 2:1) 22,23,38 and to plasmid DNA (w:w = 0.6-0.8:1). 24 The PEN vehicle could completely retard ODN MT01 at a mass ratio of 0.5. 16 Similarly, N-Ac-L-Leu-PEI leads to better cell viability than PEI25K in RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

“…21 N-Ac-L-Leu-PEI did not result in a more efficient delivery of CpG ODN, as shown in Figure 1C that the transfection efficiency was both more than 90% in the ODNs group and the N-Ac-L-Leu-PEI/CpG ODN 2006 group. Besides, it enabled CpG ODN to play a negative role in osteoclastogenesis in vitro, 23,38 which indicated the significant downregulation of proliferation and differentiation of osteoclast precursors. The lowest cell viability and more apoptotic cells were found in the N-Ac-L-Leu-PEI/CpG ODN 2006 group in our study.…”

Section: Discussionmentioning

confidence: 99%

“…N-Ac-L-Leu-PEI significantly improved the biocompatibility and transfection efficiency, and significantly decreased protein adsorption and hemolytic activity of the PEI25K matrix. This vehicle has been successfully used to deliver the p53 gene, 21 a DNAzyme 22 and microRNA 23,24 to trigger the pronounced suppression of tumor cells and to upregulate bone formation in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

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N-Acetyl-l-Leucine-Polyethyleneimine-Mediated Delivery of CpG Oligodeoxynucleotides 2006 Inhibits RAW264.7 Cell Osteoclastogenesis

Wang

et al. 2020

DDDT

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Introduction: CpG oligodeoxynucleotides (CpG ODN) play important roles in resisting inflammation and bone resorption. However, the inherent instability and rapid degradation hinder their wider application. This study aimed to evaluate whether N-acetyl-L-leucinemodified polyethyleneimine (N-Ac-L-Leu-PEI) could effectively deliver CpG ODN 2006 to RAW264.7 cells and and if it can regulate osteoclastogenesis in vitro. Materials and Methods: Gel retardation assay was conducted to evaluate whether N-Ac-L-Leu-PEI and CpG ODN could form a stable complex. RAW264.7 cells were divided into four groups of control group, ODN group, phosphorothioate ODN group and N-Ac-L-Leu-PEI/ODN group. Fluorescence assay was conducted to evaluate the transfection rate of ODNs in different groups. Cell viability was determined by MTT assay. Cell apoptosis was determined by live-dead cell staining and flow cytometry assay. Relative expression levels of osteoclastic differentiation factors, including Nfatc, c-fos, receptor activator of nuclear factor κB (RANK), and matrix metalloproteinase 9 (MMP9), were determined by real-time PCR and Western blot. Results: N-Ac-L-Leu-PEI and CpG ODN could form a stable complex at a mass ratio of 1:1 (w:w). MTT assay showed that the cell viability of N-Ac-L-Leu-PEI was relatively high even at a mass ratio of 8 μg/mL. The transfection rate of N-Ac-L-Leu-PEI-ODN complex was higher than 90%. The cell proliferation and apoptosis was significantly enhanced in N-Ac-L-Leu-PEI-CpG ODN group when compared to those in phosphorothioate CpG ODN. The expression levels of Nfatc, c-fos, RANK, and MMP9 were significantly decreased in N-Ac-L-Leu-PEI/ODN complex group. Discussion: N-Ac-L-Leu-PEI could be a potential gene vehicle for the prevention of periodontitis-mediated bone resorption.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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N-Acetyl-l-Leucine-Polyethyleneimine-Mediated Delivery of CpG Oligodeoxynucleotides 2006 Inhibits RAW264.7 Cell Osteoclastogenesis

Wang

et al. 2020

DDDT

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Conventional and hybrid nanoparticulate systems for the treatment of hepatocellular carcinoma: An updated review

Kabil

Nasr

El‐Sherbiny

2021

European Journal of Pharmaceutics and Biopharmaceutics

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Solubility Measurement, Correlation, and Thermodynamic Analysis of N-Acetyl-l-leucine in 12 Pure Organic Solvents from 283.15 to 323.15 K

Guo

Wang

et al. 2020

J. Chem. Eng. Data

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The solubility of N-acetyl-l-leucine in 12 mono organic solvents (methanol, ethanol, n-propanol, 2-propanol, 1-butanol, isobutanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, acetone, and acetonitrile) was determined by the gravimetric method over the temperatures ranging from 283.15 to 323.15 K at 0.1 MPa. The solubility of N-acetyl-l-leucine in each experimental solvent increases with increasing temperature. Moreover, the solubility is an order of magnitude higher in alcohol solvents than in other solvents, which is mainly attributed to the hydrogen bond formation. In addition, the experimental solubility data are correlated by three models, including the modified Apelblat equation, λh equation, and the nonrandom two-liquid (NRTL) model. All of the average relative deviation % values are less than 3.72%, which indicates that the three models have satisfactory correlations. Furthermore, the mixing thermodynamic properties of N-acetyl-l-leucine in 12 mono solvents including Δmix G 0, Δmix H 0, and Δmix S 0 are calculated based on the NRTL model, indicating that the mixing process was spontaneous.

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N-Acetyl-l-leucine-polyethylenimine-mediated miR-34a delivery improves osteogenesis and bone formationin vitroandin vivo

Abstract: We employ N-acetyl-l-leucine-modified polyethylenimine as an miR-34a carrier and evaluate its delivery ability, transfection efficiency, cytotoxicity and whether it enhances osteogenic differentiation and bone formation in vitro and in vivo.

Cited by 5 publications

References 31 publications

<p><em>N</em>-Acetyl-l-Leucine-Polyethyleneimine-Mediated Delivery of CpG Oligodeoxynucleotides 2006 Inhibits RAW264.7 Cell Osteoclastogenesis</p>

<p><em>N</em>-Acetyl-l-Leucine-Polyethyleneimine-Mediated Delivery of CpG Oligodeoxynucleotides 2006 Inhibits RAW264.7 Cell Osteoclastogenesis</p>

Conventional and hybrid nanoparticulate systems for the treatment of hepatocellular carcinoma: An updated review

Solubility Measurement, Correlation, and Thermodynamic Analysis of N-Acetyl-l-leucine in 12 Pure Organic Solvents from 283.15 to 323.15 K

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