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Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice
dc.contributor.author | Yang, Jun | |
dc.contributor.author | Xie, Sheng-Xue | |
dc.contributor.author | Huang, Yiling | |
dc.contributor.author | Ling, Min | |
dc.contributor.author | Liu, Jihong | |
dc.contributor.author | Ran, Yali | |
dc.contributor.author | Wang, Yanlin | |
dc.contributor.author | Thrasher, J. Brantley | |
dc.contributor.author | Berkland, Cory J. | |
dc.contributor.author | Li, Benyi | |
dc.date.accessioned | 2017-06-23T21:09:47Z | |
dc.date.available | 2017-06-23T21:09:47Z | |
dc.date.issued | 2012-09 | |
dc.identifier.citation | Yang, J., Xie, S.-X., Huang, Y., Ling, M., Liu, J., Ran, Y., … Li, B. (2012). Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice. Nanomedicine (London, England), 7(9), 1297–1309. http://doi.org/10.2217/nnm.12.14 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24597 | |
dc.description.abstract | BACKGROUND: Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft tumor eradication. In this study, we utilized a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct specifically to prostate cancer cells. MATERIALS & METHODS: The biodegradable nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer and the AR shRNA constructs were loaded inside the particles. The surface of the nanoparticles were then conjugated with prostate-specific membrane antigen aptamer A10 for prostate cancer cell-specific targeting. RESULTS: A10-conjugation largely enhanced cellular uptake of nanoparticles in both cell culture- and xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was evaluated in xenograft models with different prostate cancer cell lines: 22RV1, LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid tumor regression was observed over 2 weeks. Consistent with previous reports, A10 aptamer conjugation significantly enhanced xenograft tumor regression compared with nonconjugated nanoparticles. DISCUSSION: These data demonstrated that tissue-specific delivery of AR shRNA using a biodegradable nanoparticle approach represents a novel therapy for life-threatening prostate cancers. | en_US |
dc.publisher | Future Medicine | en_US |
dc.subject | Androgen receptor | en_US |
dc.subject | Aptamer | en_US |
dc.subject | Nanoparticle | en_US |
dc.subject | Prostate cancer | en_US |
dc.subject | Prostate-specific membrane antigen | en_US |
dc.subject | siRNA | en_US |
dc.title | Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Xie, Sheng-Xue | |
kusw.kuauthor | Berkland, Cory J. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.2217/nnm.12.14 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3448843 | en_US |
dc.rights.accessrights | openAccess |