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PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma

View Article: PubMed Central - PubMed

ABSTRACT

Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo, to inhibit HCC progression. In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent LipofectamineTM2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.

No MeSH data available.


(A) In vitro release properties of miR-99a-PEAL-LA NPs and miR-99a-mPEG-PEAL-LA/VEGFab NPs at 37 °C; Data are presented as the means ± S.D. (n = 3). (B) In vitro cytotoxicity of PEAL-LA NPs and PEAL-LA-VEGFab NPs after incubation with HepG2 cells for 24 h. Data are presented as the means ± S.D. (n = 6).
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f2: (A) In vitro release properties of miR-99a-PEAL-LA NPs and miR-99a-mPEG-PEAL-LA/VEGFab NPs at 37 °C; Data are presented as the means ± S.D. (n = 3). (B) In vitro cytotoxicity of PEAL-LA NPs and PEAL-LA-VEGFab NPs after incubation with HepG2 cells for 24 h. Data are presented as the means ± S.D. (n = 6).

Mentions: We next tested the in vitro toxicity of NPs in HepG2 cells using the CCK-8 assay. We observed no obvious changes in cell viability in cells treated with either PEAL-LA NPs or PEAL-LA/VEGFab NPs compared with cells treated with PBS after a 24-h incubation (Fig. 2B). Even with exposure to higher NP concentrations (200 μg/mL), more than 80% of cells remained viable, which suggests that both PEAL-LA NPs and PEAL-LA/VEGFab NPs exert negligible toxicity and are highly compatible with living cells.


PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma
(A) In vitro release properties of miR-99a-PEAL-LA NPs and miR-99a-mPEG-PEAL-LA/VEGFab NPs at 37 °C; Data are presented as the means ± S.D. (n = 3). (B) In vitro cytotoxicity of PEAL-LA NPs and PEAL-LA-VEGFab NPs after incubation with HepG2 cells for 24 h. Data are presented as the means ± S.D. (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384185&req=5

f2: (A) In vitro release properties of miR-99a-PEAL-LA NPs and miR-99a-mPEG-PEAL-LA/VEGFab NPs at 37 °C; Data are presented as the means ± S.D. (n = 3). (B) In vitro cytotoxicity of PEAL-LA NPs and PEAL-LA-VEGFab NPs after incubation with HepG2 cells for 24 h. Data are presented as the means ± S.D. (n = 6).
Mentions: We next tested the in vitro toxicity of NPs in HepG2 cells using the CCK-8 assay. We observed no obvious changes in cell viability in cells treated with either PEAL-LA NPs or PEAL-LA/VEGFab NPs compared with cells treated with PBS after a 24-h incubation (Fig. 2B). Even with exposure to higher NP concentrations (200 μg/mL), more than 80% of cells remained viable, which suggests that both PEAL-LA NPs and PEAL-LA/VEGFab NPs exert negligible toxicity and are highly compatible with living cells.

View Article: PubMed Central - PubMed

ABSTRACT

Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo, to inhibit HCC progression. In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent LipofectamineTM2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.

No MeSH data available.