| Title |
A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells
|
|---|---|
| Published in |
International Journal of Nanomedicine, March 2013
|
| DOI | 10.2147/ijn.s41555 |
| Pubmed ID | |
| Authors |
Guanhua Li, Zuojun Hu, Henghui Yin, Yunjian Zhang, Xueling Huang, Shenming Wang, Wen Li |
| Abstract |
The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA) delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG) in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and gel retardation assay confirmed that complete triblock components were successfully synthesized with effective binding capacity of siRNA in this triblock nanocarrier. Cytotoxicity data indicated that conjugation of PEG significantly alleviated cytotoxicity when compared with unmodified PAMAM. PAMAM-PEG-cRGD exerted potent siRNA cellular internalization in which transfection efficiency measured by flow cytometry was up to 68% when the charge ratio (N/P ratio) was 3.5. Ligand-receptor affinity together with electrostatic interaction should be involved in the nano-siRNA endocytosis mechanism and we then proved that attachment of cRGD enhanced cellular uptake via RGD-integrin recognition. Gene silencing was evaluated by reverse transcription polymerase chain reaction and PAMAM-PEG-cRGD-siRNA complex downregulated the expression of hERG to 26.3% of the control value. Furthermore, gene knockdown of hERG elicited growth suppression as well as activated apoptosis by means of abolishing vascular endothelial growth factor secretion and triggering caspase-3 cascade in anaplastic thyroid carcinoma cells. Our study demonstrates that this novel triblock polymer, PAMAM-PEG-cRGD, exhibits negligible cytotoxicity, effective transfection, "smart" cancer targeting, and therefore is a promising siRNA nanocarrier. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Austria | 1 | 3% |
| Unknown | 29 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 33% |
| Researcher | 8 | 27% |
| Student > Bachelor | 4 | 13% |
| Student > Master | 3 | 10% |
| Student > Doctoral Student | 3 | 10% |
| Other | 0 | 0% |
| Unknown | 2 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 7 | 23% |
| Chemistry | 5 | 17% |
| Medicine and Dentistry | 5 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 10% |
| Chemical Engineering | 1 | 3% |
| Other | 5 | 17% |
| Unknown | 4 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 April 2013.
All research outputs
#19,945,185
of 25,374,917 outputs
Outputs from International Journal of Nanomedicine
#2,970
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Outputs of similar age
#152,660
of 206,326 outputs
Outputs of similar age from International Journal of Nanomedicine
#44
of 66 outputs
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