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PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells.

Liang GF, Zhu YL, Sun B, Hu FH, Tian T, Li SC, Xiao ZD - Nanoscale Res Lett (2011)

Bottom Line: The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes.Moreover, nanocomplex shows better serum compatibility than commercial liposome.Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China. zdxiao@seu.edu.

ABSTRACT
The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

No MeSH data available.


Related in: MedlinePlus

Cell cycle profiles of PLGA-based nanoparticles transfected HepG2 cells. Numbers in Table 3 indicate the percentage of cells remaining in each phase of cell cycle. (A) Untreated group; (B) miR-NC contained nanoparticles transfected HepG2 cells; (C) miR-26a contained nanoparticles transfected HepG2 cells. Table 3 numbered cell cycle profiles corresponding to this figure.
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Figure 6: Cell cycle profiles of PLGA-based nanoparticles transfected HepG2 cells. Numbers in Table 3 indicate the percentage of cells remaining in each phase of cell cycle. (A) Untreated group; (B) miR-NC contained nanoparticles transfected HepG2 cells; (C) miR-26a contained nanoparticles transfected HepG2 cells. Table 3 numbered cell cycle profiles corresponding to this figure.

Mentions: The miR-26a-containing PLGA-based nanocomposites significantly increase the expression level of miR-26a and inhibit the cell cycle progression by induction of G1 phase arrested in transfected HepG2 cells, whereas the effect in control groups (miRNA negative control transfected cells) were not detectable. Figure 6C indicates that cell populations with enforced miR-26a expression were characterized by significantly increased numbers of cells arrested in G1, which is more than that of tumor cells treated with miR-NC containing PLGA nanocomplex or untreated control (Table 3). Kota et al. have demonstrated that upregulation of miR-26a expression results in the inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and enhancement of antitumor activity [3]. In this study, we have developed a PLGA-based nanocomplex and tested its gene delivery ability on HepG2 cells. Our studies demonstrate that PLGA nanocomplex facilitated cellular uptake and enhanced gene expression activity.


PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells.

Liang GF, Zhu YL, Sun B, Hu FH, Tian T, Li SC, Xiao ZD - Nanoscale Res Lett (2011)

Cell cycle profiles of PLGA-based nanoparticles transfected HepG2 cells. Numbers in Table 3 indicate the percentage of cells remaining in each phase of cell cycle. (A) Untreated group; (B) miR-NC contained nanoparticles transfected HepG2 cells; (C) miR-26a contained nanoparticles transfected HepG2 cells. Table 3 numbered cell cycle profiles corresponding to this figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3211866&req=5

Figure 6: Cell cycle profiles of PLGA-based nanoparticles transfected HepG2 cells. Numbers in Table 3 indicate the percentage of cells remaining in each phase of cell cycle. (A) Untreated group; (B) miR-NC contained nanoparticles transfected HepG2 cells; (C) miR-26a contained nanoparticles transfected HepG2 cells. Table 3 numbered cell cycle profiles corresponding to this figure.
Mentions: The miR-26a-containing PLGA-based nanocomposites significantly increase the expression level of miR-26a and inhibit the cell cycle progression by induction of G1 phase arrested in transfected HepG2 cells, whereas the effect in control groups (miRNA negative control transfected cells) were not detectable. Figure 6C indicates that cell populations with enforced miR-26a expression were characterized by significantly increased numbers of cells arrested in G1, which is more than that of tumor cells treated with miR-NC containing PLGA nanocomplex or untreated control (Table 3). Kota et al. have demonstrated that upregulation of miR-26a expression results in the inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and enhancement of antitumor activity [3]. In this study, we have developed a PLGA-based nanocomplex and tested its gene delivery ability on HepG2 cells. Our studies demonstrate that PLGA nanocomplex facilitated cellular uptake and enhanced gene expression activity.

Bottom Line: The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes.Moreover, nanocomplex shows better serum compatibility than commercial liposome.Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China. zdxiao@seu.edu.

ABSTRACT
The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

No MeSH data available.


Related in: MedlinePlus