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Updated: Jul 17, 2026
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
An antisense oligonucleotide carrier based on amino silica nanoparticles for antisense inhibition of cancer cells
Jiaofeng Peng1, Xiaoxiao He, Kemin Wang
1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Research Center of Bio-nanotechnology Engineering in Hunan Province, Changsha, China.
Abstract:
Antisense oligonucleotides (anti-ODNs), which are able to interfere with gene expression at the mRNA level, have potential activity in the treatment of viral infections or cancer. However, the application of therapies based on anti-ODNs is hampered by their instability to cellular nuclease and their weak intracellular penetration. Among the many efforts to increase their stability and cellular penetration have been modifications of ODNs and introduction of particulate carriers. Here we report an anti-ODNs carrier based on amino silica nanoparticles (NH(2)SiNPs) and its preliminary applications in cancer cells. The positively charged NH(2)SiNPs were synthesized by a water-in-oil microemulsion method. The NH(2)SiNP-ODN complexes were formed by electrostatic interaction, and their cellular uptake was visualized by using fluorescein isothiocyanate (FITC)-labeled ODNs and NH(2)SiNPs doped with rhodamine 6G isothiocyanate (RITC) as fluorescent signal indicators. The antisense inhibition efficiency of anti-ODNs delivered by NH(2)SiNPs was evaluated using MTT (3,4,5-dimethylthiazol-2,5-diphenyl tetrazolium bromide) assay and western blot analysis. Uniform NH(2)SiNPs with an average diameter of 25 nm were obtained and could combine with anti-ODNs to form a bioconjugate favorable for cellular uptake. The NH(2)SiNPs were able to protect anti-ODNs from degradation by DNase I. In vitro experiments showed that the NH(2)SiNPs could greatly improve the inhibition efficiency of anti-ODNs for the proliferation and survivin expression in Hela cells and A549 cells. Compared with liposomes, the NH(2)SiNPs presented a better biocompatibility and had almost no cytotoxicity at the concentrations required for efficient transfection. Our results suggest that the NH(2)SiNPs may be a promising carrier for delivery of anti-ODNs.
Insights
Amino silica nanoparticles (NH2SiNPs) effectively deliver antisense oligonucleotides (anti-ODNs) into cancer cells, enhancing their therapeutic potential by improving stability and cellular uptake. This novel delivery system shows promise for cancer treatment applications.
Area of Science:
- Biotechnology and Nanomedicine
- Molecular Biology and Genetics
- Materials Science
Background:
- Antisense oligonucleotides (anti-ODNs) show therapeutic potential for viral infections and cancer by interfering with gene expression.
- Current limitations of anti-ODN therapy include poor stability against cellular nucleases and inefficient intracellular penetration.
- Particulate carriers and chemical modifications are being explored to enhance anti-ODN delivery and efficacy.
Purpose of the Study:
- To develop and evaluate amino silica nanoparticles (NH2SiNPs) as a novel carrier for antisense oligonucleotides (anti-ODNs).
- To assess the stability, cellular uptake, and therapeutic efficacy of anti-ODNs delivered by NH2SiNPs in cancer cells.
- To compare the biocompatibility and cytotoxicity of NH2SiNPs with traditional carriers like liposomes.
Main Methods:
- Synthesis of positively charged amino silica nanoparticles (NH2SiNPs) using a water-in-oil microemulsion method.
- Formation of NH2SiNP-anti-ODN complexes via electrostatic interactions.
- Evaluation of cellular uptake using fluorescently labeled NH2SiNPs and anti-ODNs.
- Assessment of anti-ODN stability against DNase I degradation.
- Measurement of antisense inhibition efficiency using MTT assays and Western blot analysis in Hela and A549 cells.
Main Results:
- Uniform 25 nm NH2SiNPs were synthesized and successfully formed bioconjugates with anti-ODNs, enhancing cellular uptake.
- NH2SiNPs protected anti-ODNs from DNase I degradation, significantly improving their stability.
- NH2SiNP-mediated delivery of anti-ODNs markedly enhanced inhibition of proliferation and survivin expression in cancer cells.
- NH2SiNPs demonstrated superior biocompatibility and minimal cytotoxicity compared to liposomes at effective transfection concentrations.
Conclusions:
- Amino silica nanoparticles (NH2SiNPs) serve as an effective and biocompatible carrier for antisense oligonucleotides (anti-ODNs).
- NH2SiNP-based delivery significantly enhances the stability and intracellular delivery of anti-ODNs, leading to improved therapeutic efficacy in cancer cells.
- NH2SiNPs represent a promising nanocarrier for the development of advanced anti-ODN therapies with reduced toxicity.
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