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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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The expression and distribution of VHL protein in RCC tissues via FA-PEAs mediated gene therapy. (A)-(C) was respectively represented the PBS group, the pVITRO2 group and the VHL-treated group. The staining profiling was observed under 400 × magnification. The scale bar represents 200 μm.
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Figure 6: The expression and distribution of VHL protein in RCC tissues via FA-PEAs mediated gene therapy. (A)-(C) was respectively represented the PBS group, the pVITRO2 group and the VHL-treated group. The staining profiling was observed under 400 × magnification. The scale bar represents 200 μm.

Mentions: Furthermore, IHC was performed to analyze the expression and distribution of VHL protein among the three groups. As shown in Figure 6, the VHL protein was abundantly expressed in cytoplasm in the VHL-treated group (Figure 6C). While under same the conditions, few or no expression activity was observed in the tumor tissues in PBS group and pVITRO2 group (Figure 6A-6B). Generally, the target gene VHL was transferred into tumor area by FA-PEAs to suppress tumor growth.


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)

The expression and distribution of VHL protein in RCC tissues via FA-PEAs mediated gene therapy. (A)-(C) was respectively represented the PBS group, the pVITRO2 group and the VHL-treated group. The staining profiling was observed under 400 × magnification. The scale bar represents 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: The expression and distribution of VHL protein in RCC tissues via FA-PEAs mediated gene therapy. (A)-(C) was respectively represented the PBS group, the pVITRO2 group and the VHL-treated group. The staining profiling was observed under 400 × magnification. The scale bar represents 200 μm.
Mentions: Furthermore, IHC was performed to analyze the expression and distribution of VHL protein among the three groups. As shown in Figure 6, the VHL protein was abundantly expressed in cytoplasm in the VHL-treated group (Figure 6C). While under same the conditions, few or no expression activity was observed in the tumor tissues in PBS group and pVITRO2 group (Figure 6A-6B). Generally, the target gene VHL was transferred into tumor area by FA-PEAs to suppress tumor growth.

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