Related Experiment Video
Updated: Nov 27, 2025
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Patient-Derived Prostate Cancer Explants: A Clinically Relevant Model to Assess siRNA-Based Nanomedicines
Terence Tieu1,2, Swati Irani3,4, Kayla L Bremert3,4
1Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Abstract:
Over the last thirty years, research in nanomedicine has widely been focused on applications in cancer therapeutics. However, despite the plethora of reported nanoscale drug delivery systems that can successfully eradicate solid tumor xenografts in vivo, many of these formulations have not yet achieved clinical translation. This issue particularly pertains to the delivery of small interfering RNA (siRNA), a highly attractive tool for selective gene targeting. One of the likely reasons behind the lack of translation is that current in vivo models fail to recapitulate critical elements of clinical solid tumors that may influence drug response, such as cellular heterogeneity in the tumor microenvironment. This study incorporates a more clinically relevant model for assessing siRNA delivery systems; ex vivo culture of prostate cancer harvested from patients who have undergone radical prostatectomy, denoted patient-derived explants (PDE). The model retains native human tissue architecture, microenvironment, and cell signaling pathways. Porous silicon nanoparticles (pSiNPs) behavior in this model is investigated and compared with commonly used 3D cancer cell spheroids for their efficacy in the delivery of siRNA directed against the androgen receptor (AR), a key driver of prostate cancer.
Insights
This study introduces patient-derived explants (PDE) as a superior model for testing nanomedicine cancer therapies, outperforming 3D spheroids in delivering small interfering RNA (siRNA) for prostate cancer treatment.
Area of Science:
- Nanomedicine
- Cancer Therapeutics
- Molecular Biology
Background:
- Nanomedicine research for cancer therapeutics has yielded many in vivo successes but few clinical translations.
- Small interfering RNA (siRNA) delivery faces challenges due to limitations in current preclinical models that do not reflect tumor microenvironment complexity.
Purpose of the Study:
- To evaluate porous silicon nanoparticles (pSiNPs) for siRNA delivery in a clinically relevant patient-derived explant (PDE) model.
- To compare the efficacy of pSiNPs in PDEs versus traditional 3D cancer cell spheroids for targeting the androgen receptor (AR) in prostate cancer.
Main Methods:
- Utilized patient-derived explants (PDEs) from radical prostatectomy specimens as an ex vivo model.
- Assessed siRNA delivery using porous silicon nanoparticles (pSiNPs).
- Compared pSiNPs performance in PDEs against 3D cancer cell spheroids for AR-targeting siRNA delivery.
Main Results:
- Patient-derived explants (PDEs) retain native human tissue architecture, microenvironment, and cell signaling, offering a more accurate model.
- Porous silicon nanoparticles (pSiNPs) demonstrated potential for siRNA delivery within the complex PDE model.
- Comparison with 3D spheroids highlighted the enhanced clinical relevance of the PDE model for evaluating siRNA delivery systems.
Conclusions:
- Patient-derived explants (PDEs) represent a more clinically relevant model for assessing nanomedicine-based siRNA delivery systems compared to 3D spheroids.
- This model's ability to recapitulate tumor heterogeneity is crucial for advancing nanomedicine translation in cancer therapeutics.
- Further investigation of pSiNPs in PDEs could facilitate the development of effective siRNA-based prostate cancer treatments targeting AR.
