| Autor: |
Justin B Lee, Kaixin Zhang, Yuen Yi C Tam, Joslyn Quick, Ying K Tam, Paulo JC Lin, Sam Chen, Yan Liu, Jayaprakash K Nair, Ivan Zlatev, Kallanthottathil G Rajeev, Muthiah Manoharan, Paul S Rennie, Pieter R Cullis |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 5, Iss C (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1038/mtna.2016.43 |
| Popis: |
The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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