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Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes.

Zhang W, Peng F, Zhou T, Huang Y, Zhang L, Ye P, Lu M, Yang G, Gai Y, Yang T, Ma X, Xiang G - Int J Nanomedicine (2015)

Bottom Line: Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro.Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27(kip1), and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome.After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27(kip1), and TIMP3.

View Article: PubMed Central - PubMed

Affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27(kip1), and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27(kip1), and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC.

No MeSH data available.


Related in: MedlinePlus

In vivo evaluation of the effect of anti-miR-221 treatments on target gene expressions in a xenograft model of HepG2 human liver cancer.Notes: Female BALB/c-nu mice were treated with 1.2 mg/kg of Tf-RL and RL for 48 hours. Tumors were harvested, and the target gene expressions were determined by RT-PCR. Control group was treated with saline. Each value represents the mean ± standard deviation (n=3). *P<0.05.Abbreviations: RL, nontargeted liposome containing anti-miR-221; Tf-RL, transferrin-targeted liposome containing anti-miR-221; RT-PCR, real-time polymerase chain reaction.
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f8-ijn-10-4825: In vivo evaluation of the effect of anti-miR-221 treatments on target gene expressions in a xenograft model of HepG2 human liver cancer.Notes: Female BALB/c-nu mice were treated with 1.2 mg/kg of Tf-RL and RL for 48 hours. Tumors were harvested, and the target gene expressions were determined by RT-PCR. Control group was treated with saline. Each value represents the mean ± standard deviation (n=3). *P<0.05.Abbreviations: RL, nontargeted liposome containing anti-miR-221; Tf-RL, transferrin-targeted liposome containing anti-miR-221; RT-PCR, real-time polymerase chain reaction.

Mentions: In order to determine the delivery efficiency of Tf-RL in vivo, the expressions of target genes PTEN, P27kip1, and TIMP3 were evaluated in vivo by RT-PCR. Tf-RL and RL were given to each mouse at a single dose of 1.2 mg/kg through tail vein iv injection. After 48 hours postadministration, the mice were sacrificed and their tissues were harvested. The expressions of target genes PTEN, P27kip1, and TIMP3 were evaluated by RT-PCR (Figure 8). As expected, the expressions were increased in Tf-RL- and RL-treated groups, compared to the untreated group, while Tf-RL group had a higher increase than RL group. These data demonstrate superior delivery efficiency by Tf-RL, and corroborate the results of our in vitro experiments.


Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes.

Zhang W, Peng F, Zhou T, Huang Y, Zhang L, Ye P, Lu M, Yang G, Gai Y, Yang T, Ma X, Xiang G - Int J Nanomedicine (2015)

In vivo evaluation of the effect of anti-miR-221 treatments on target gene expressions in a xenograft model of HepG2 human liver cancer.Notes: Female BALB/c-nu mice were treated with 1.2 mg/kg of Tf-RL and RL for 48 hours. Tumors were harvested, and the target gene expressions were determined by RT-PCR. Control group was treated with saline. Each value represents the mean ± standard deviation (n=3). *P<0.05.Abbreviations: RL, nontargeted liposome containing anti-miR-221; Tf-RL, transferrin-targeted liposome containing anti-miR-221; RT-PCR, real-time polymerase chain reaction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524461&req=5

f8-ijn-10-4825: In vivo evaluation of the effect of anti-miR-221 treatments on target gene expressions in a xenograft model of HepG2 human liver cancer.Notes: Female BALB/c-nu mice were treated with 1.2 mg/kg of Tf-RL and RL for 48 hours. Tumors were harvested, and the target gene expressions were determined by RT-PCR. Control group was treated with saline. Each value represents the mean ± standard deviation (n=3). *P<0.05.Abbreviations: RL, nontargeted liposome containing anti-miR-221; Tf-RL, transferrin-targeted liposome containing anti-miR-221; RT-PCR, real-time polymerase chain reaction.
Mentions: In order to determine the delivery efficiency of Tf-RL in vivo, the expressions of target genes PTEN, P27kip1, and TIMP3 were evaluated in vivo by RT-PCR. Tf-RL and RL were given to each mouse at a single dose of 1.2 mg/kg through tail vein iv injection. After 48 hours postadministration, the mice were sacrificed and their tissues were harvested. The expressions of target genes PTEN, P27kip1, and TIMP3 were evaluated by RT-PCR (Figure 8). As expected, the expressions were increased in Tf-RL- and RL-treated groups, compared to the untreated group, while Tf-RL group had a higher increase than RL group. These data demonstrate superior delivery efficiency by Tf-RL, and corroborate the results of our in vitro experiments.

Bottom Line: Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro.Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27(kip1), and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome.After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27(kip1), and TIMP3.

View Article: PubMed Central - PubMed

Affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27(kip1), and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27(kip1), and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC.

No MeSH data available.


Related in: MedlinePlus