| Title |
Novel delivery system for T-oligo using a nanocomplex formed with an alpha helical peptide for melanoma therapy
|
|---|---|
| Published in |
International Journal of Nanomedicine, December 2013
|
| DOI | 10.2147/ijn.s55133 |
| Pubmed ID | |
| Authors |
Srijayaprakash B Uppada, Terrianne Erickson, Luke Wojdyla, David N Moravec, Ziyuan Song, Jianjun Cheng, Neelu Puri |
| Abstract |
Oligonucleotides homologous to 3'-telomere overhang (T-oligos) trigger inherent telomere-based DNA damage responses mediated by p53 and/or ATM and induce senescence or apoptosis in various cancerous cells. However, T-oligo has limited stability in vivo due to serum and intracellular nucleases. To develop T-oligo as an innovative, effective therapeutic drug and to understand its mechanism of action, we investigated the antitumor effects of T-oligo or T-oligo complexed with a novel cationic alpha helical peptide, PVBLG-8 (PVBLG), in a p53 null melanoma cell line both in vitro and in vivo. The uptake of T-oligo by MM-AN cells was confirmed by immunofluorescence, and fluorescence-activated cell sorting analysis indicated that the T-oligo-PVBLG nanocomplex increased uptake by 15-fold. In vitro results showed a 3-fold increase in MM-AN cell growth inhibition by the T-oligo-PVBLG nanocomplex compared with T-oligo alone. Treatment of preformed tumors in immunodeficient mice with the T-oligo-PVBLG nanocomplex resulted in a 3-fold reduction in tumor volume compared with T-oligo alone. This reduction in tumor volume was associated with decreased vascular endothelial growth factor expression and induction of thrombospondin-1 expression and apoptosis. Moreover, T-oligo treatment downregulated procaspase-3 and procaspase-7 and increased catalytic activity of caspase-3 by 4-fold in MM-AN cells. Furthermore, T-oligo induced a 10-fold increase of senescence and upregulated the melanoma tumor-associated antigens MART-1, tyrosinase, and thrombospondin-1 in MM-AN cells, which are currently being targeted for melanoma immunotherapy. Interestingly, siRNA-mediated knockdown of p73 (4-10-fold) abolished this upregulation of tumor-associated antigens. In summary, we suggest a key role of p73 in mediating the anticancer effects of T-oligo and introduce a novel nanoparticle, the T-oligo-PVBLG nanocomplex, as an effective anticancer therapeutic. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 17 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 35% |
| Student > Bachelor | 3 | 18% |
| Lecturer > Senior Lecturer | 1 | 6% |
| Other | 1 | 6% |
| Unspecified | 1 | 6% |
| Other | 3 | 18% |
| Unknown | 2 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 41% |
| Agricultural and Biological Sciences | 5 | 29% |
| Unspecified | 1 | 6% |
| Chemistry | 1 | 6% |
| Medicine and Dentistry | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 2 | 12% |
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 17 December 2013.
All research outputs
#17,285,668
of 25,374,647 outputs
Outputs from International Journal of Nanomedicine
#2,469
of 4,123 outputs
Outputs of similar age
#205,368
of 320,965 outputs
Outputs of similar age from International Journal of Nanomedicine
#84
of 101 outputs
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