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Updated: Mar 28, 2026
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
A novel, anisamide-targeted cyclodextrin nanoformulation for siRNA delivery to prostate cancer cells expressing the
Kathleen A Fitzgerald1, Meenakshi Malhotra1, Matt Gooding2
1Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland.
Abstract:
Prostate cancer is a leading cause of cancer-related death in men and RNA interference (RNAi) has emerged as a potential therapeutic option. However, the absence of a safe and specific delivery vector remains a major obstacle to the clinical application of RNAi. Cyclodextrin derivatives are known to be efficient delivery systems with low toxicity in a variety of cell types. In this study, a cationic cyclodextrin derivative was synthesized to complex siRNA. The nanoparticle was then further modified by exploiting the ability of the β-cyclodextrin cavity to form an inclusion complex with the hydrophobic molecule adamantane. PEGylated adamantane derivatives were synthesized with and without the anisamide-targeting ligand on the terminal end of the PEG chain. Anisamide is known to bind specifically to the sigma receptor which is overexpressed on the surface of prostate cancer cells. The resulting nanocomplexes were slightly cationic and less than 300 nm in size. They successfully protected siRNA from serum-induced nuclease degradation and were non-toxic to prostate cancer cells. In addition, the targeted nanoparticles mediated high levels of siRNA cellular uptake and corresponding PLK1 gene knockdown in prostate cancer cells in vitro. To our knowledge, this is the first time that the ability of cyclodextrins to form inclusion complexes with adamantane derivatives has been exploited for the targeted delivery of siRNA to prostate cancer cells via the sigma receptor.
Insights
Researchers developed a novel nanoparticle for targeted prostate cancer therapy using RNA interference (RNAi). This new delivery system effectively targets cancer cells and reduces PLK1 gene expression, offering a promising avenue for treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Prostate cancer is a significant cause of male cancer mortality.
- RNA interference (RNAi) shows therapeutic potential but lacks effective delivery vectors.
- Cyclodextrin derivatives offer a low-toxicity delivery system for therapeutic applications.
Purpose of the Study:
- To synthesize and characterize a novel cationic cyclodextrin-based nanoparticle for siRNA delivery.
- To functionalize the nanoparticle with anisamide for targeted delivery to prostate cancer cells via sigma receptors.
- To evaluate the nanoparticle's efficacy in protecting siRNA and achieving gene knockdown in vitro.
Main Methods:
- Synthesis of a cationic cyclodextrin derivative complexed with siRNA.
- Modification of the nanoparticle with PEGylated adamantane derivatives, including an anisamide-targeting ligand.
- Characterization of nanocomplex size, charge, siRNA protection, and cytotoxicity.
- In vitro assessment of cellular uptake and PLK1 gene knockdown in prostate cancer cells.
Main Results:
- The resulting nanocomplexes were <300 nm, slightly cationic, and protected siRNA from degradation.
- The targeted nanoparticles demonstrated no toxicity to prostate cancer cells.
- Anisamide-functionalized nanoparticles achieved significant siRNA cellular uptake and PLK1 gene knockdown in vitro.
Conclusions:
- This study presents a novel application of cyclodextrin-adamantane inclusion complexes for targeted siRNA delivery.
- The developed system successfully targets prostate cancer cells expressing sigma receptors.
- This approach offers a promising strategy for advancing RNA interference-based therapies for prostate cancer.
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