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Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma.

Xu Z, Shen G, Xia X, Zhao X, Zhang P, Wu H, Guo Q, Qian Z, Wei Y, Liang S - J Transl Med (2011)

Bottom Line: Each of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weight in vitro.And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models.The VHL gene expression was greatly improved in the VHL-treated group.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, P. R. China

ABSTRACT

Background: Polyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some modifications against PEI properties have been done to improve their application value in gene delivery. In this study, three modified PEI derivatives, including poly(ε-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI (PCFC-g-PEI), folic acid-PCFC-isophorone diidocyanate-PEI (FA-PEAs) and heparin-PEI (HPEI), were evaluated in terms of their cytotoxicity and transfection efficiency in vitro and in vivo in order to ascertain their potential application in gene therapy.

Methods: MTT assay and a marker GFP gene, encoding green fluorescent protein, were used to evaluate cell toxicity and transfection activity of the three modified PEI in vitro. Renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells to detect the gene therapy effects using the three PEI-derived nanoparticles as gene delivery vehicles. The expression status of a target gene Von Hippel-Lindau (VHL) in treated tumor tissues was analyzed by semiquantitative RT-PCR and immunohistochemistry.

Results: Each of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weight in vitro. And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models. The VHL gene expression was greatly improved in the VHL-treated group. While there was no obvious tumor inhibition treated by PCFC-g-PEI:VHL and HPEI:VHL complexes.

Conclusions: The three modified PEI-derived biomaterials, including PCFC-g-PEI, FA-PEAs and HPEI, had an increased transfection efficiency in vitro and obviously lower toxicities compared with their precursor PEI molecules. The FA-PEAs probably provide a potential gene delivery system to treat RCC even other cancers in future.

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Related in: MedlinePlus

Cell toxicity of several PEI-derived nanoparticles by MTT analysis. The figure A-B was shown cytotoxicity on OS-RC-2 cells, and C-D indicated viability of HUVEC cells respectively treated with PCFC-g-PEI and FA-PEAs, which was respectively compared with 25-kD and 2-kD PEI. The error bars represented the standard deviation of three repeated experiments (n = 3).
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Figure 1: Cell toxicity of several PEI-derived nanoparticles by MTT analysis. The figure A-B was shown cytotoxicity on OS-RC-2 cells, and C-D indicated viability of HUVEC cells respectively treated with PCFC-g-PEI and FA-PEAs, which was respectively compared with 25-kD and 2-kD PEI. The error bars represented the standard deviation of three repeated experiments (n = 3).

Mentions: The toxicity caused by the three PEI derivatives was primary evaluated in OS-RC-2 cell line. Compared with 25-kD PEI, 10, 20 and 30 μg/ml PCFC-g-PEI had no apparent cytotoxicity on cells. While the cell survival rate was approximately 50% under 30 μg/ml of 25-kD PEI incubation with cells. Therefore, the toxicity of PCFC-g-PEI was lower than its precursor, 25-kD PEI, for OS-RC-2 cells (Figure 1A), and the biocompatibility of PCFC-g-PEI was improved than 25-kD PEI.


Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma.

Xu Z, Shen G, Xia X, Zhao X, Zhang P, Wu H, Guo Q, Qian Z, Wei Y, Liang S - J Transl Med (2011)

Cell toxicity of several PEI-derived nanoparticles by MTT analysis. The figure A-B was shown cytotoxicity on OS-RC-2 cells, and C-D indicated viability of HUVEC cells respectively treated with PCFC-g-PEI and FA-PEAs, which was respectively compared with 25-kD and 2-kD PEI. The error bars represented the standard deviation of three repeated experiments (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108928&req=5

Figure 1: Cell toxicity of several PEI-derived nanoparticles by MTT analysis. The figure A-B was shown cytotoxicity on OS-RC-2 cells, and C-D indicated viability of HUVEC cells respectively treated with PCFC-g-PEI and FA-PEAs, which was respectively compared with 25-kD and 2-kD PEI. The error bars represented the standard deviation of three repeated experiments (n = 3).
Mentions: The toxicity caused by the three PEI derivatives was primary evaluated in OS-RC-2 cell line. Compared with 25-kD PEI, 10, 20 and 30 μg/ml PCFC-g-PEI had no apparent cytotoxicity on cells. While the cell survival rate was approximately 50% under 30 μg/ml of 25-kD PEI incubation with cells. Therefore, the toxicity of PCFC-g-PEI was lower than its precursor, 25-kD PEI, for OS-RC-2 cells (Figure 1A), and the biocompatibility of PCFC-g-PEI was improved than 25-kD PEI.

Bottom Line: Each of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weight in vitro.And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models.The VHL gene expression was greatly improved in the VHL-treated group.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, P. R. China

ABSTRACT

Background: Polyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some modifications against PEI properties have been done to improve their application value in gene delivery. In this study, three modified PEI derivatives, including poly(ε-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI (PCFC-g-PEI), folic acid-PCFC-isophorone diidocyanate-PEI (FA-PEAs) and heparin-PEI (HPEI), were evaluated in terms of their cytotoxicity and transfection efficiency in vitro and in vivo in order to ascertain their potential application in gene therapy.

Methods: MTT assay and a marker GFP gene, encoding green fluorescent protein, were used to evaluate cell toxicity and transfection activity of the three modified PEI in vitro. Renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells to detect the gene therapy effects using the three PEI-derived nanoparticles as gene delivery vehicles. The expression status of a target gene Von Hippel-Lindau (VHL) in treated tumor tissues was analyzed by semiquantitative RT-PCR and immunohistochemistry.

Results: Each of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weight in vitro. And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models. The VHL gene expression was greatly improved in the VHL-treated group. While there was no obvious tumor inhibition treated by PCFC-g-PEI:VHL and HPEI:VHL complexes.

Conclusions: The three modified PEI-derived biomaterials, including PCFC-g-PEI, FA-PEAs and HPEI, had an increased transfection efficiency in vitro and obviously lower toxicities compared with their precursor PEI molecules. The FA-PEAs probably provide a potential gene delivery system to treat RCC even other cancers in future.

Show MeSH
Related in: MedlinePlus