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A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo
- Source :
- Molecular Therapy. Nucleic Acids, Molecular Therapy: Nucleic Acids, Vol 5, Iss C (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
liposomes
Small interfering RNA
Biology
lipid nanoparticles
03 medical and health sciences
Prostate cancer
0302 clinical medicine
In vivo
androgen receptor
Drug Discovery
medicine
Liposome
Messenger RNA
lcsh:RM1-950
prostate specific membrane antigen
Ligand (biochemistry)
medicine.disease
prostate cancer
3. Good health
Androgen receptor
lcsh:Therapeutics. Pharmacology
030104 developmental biology
Biochemistry
030220 oncology & carcinogenesis
siRNA
Cancer research
Systemic administration
Molecular Medicine
Original Article
Subjects
Details
- ISSN :
- 21622531
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy - Nucleic Acids
- Accession number :
- edsair.doi.dedup.....88a79f12b9fcd0999a667aa7d682ea76
- Full Text :
- https://doi.org/10.1038/mtna.2016.43