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Updated: May 22, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft
Jun Yang1, Sheng-Xue Xie, Yiling Huang
1Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
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.
Insights
Biodegradable nanoparticles deliver androgen receptor (AR) shRNA to prostate cancer cells, leading to significant tumor regression. This targeted therapy shows promise for treating advanced prostate cancer by silencing the AR gene.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Molecular Biology
Background:
- Prostate cancer is a leading cause of cancer death in men.
- The androgen receptor (AR) is critical in prostate cancer progression.
- Previous studies showed AR gene knockdown induces apoptosis and tumor eradication.
Purpose of the Study:
- To develop a biodegradable nanoparticle system for targeted delivery of AR shRNA to prostate cancer cells.
- To evaluate the therapeutic efficacy of AR shRNA delivered via nanoparticles in preclinical models.
Main Methods:
- Biodegradable poly(dl-lactic-co-glycolic acid) nanoparticles were fabricated and loaded with AR shRNA constructs.
- Nanoparticles were conjugated with prostate-specific membrane antigen aptamer A10 for targeted delivery.
- Efficacy was assessed in cell culture and xenograft models of prostate cancer.
Main Results:
- A10 aptamer conjugation significantly enhanced nanoparticle cellular uptake.
- AR shRNA-loaded nanoparticles effectively silenced the AR gene in PC-3/AR xenografts.
- Two injections of A10-conjugated AR shRNA nanoparticles resulted in rapid tumor regression over 2 weeks in various prostate cancer models.
Conclusions:
- Tissue-specific delivery of AR shRNA using biodegradable nanoparticles is a novel therapeutic strategy.
- This approach shows significant potential for treating life-threatening prostate cancers by targeting the AR pathway.
