Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery
April 16th, 2019
We demonstrate the synthesis of fusogenic porous silicon nanoparticles for effective in vitro and in vivo oligonucleotide delivery. Porous silicon nanoparticles are loaded with siRNA to form the core, which is coated by fusogenic lipids through extrusion to form the shell. Targeting moiety functionalization and particle characterization are included.
Overview
This article presents a method for synthesizing fusogenic porous silicon nanoparticles designed for efficient oligonucleotide delivery in vitro and in vivo. The nanoparticles are engineered to carry siRNA and are coated with fusogenic lipids, enhancing their delivery capabilities.
Key Study Components
Area of Science
- Nanoparticle synthesis
- Gene delivery systems
- Therapeutic applications
Background
- Fusogenic nanoparticles can silence genes effectively.
- Targeting peptides and siRNA payloads can be customized.
- Previous studies have shown efficacy against bacterial infections.
- Chronic inflammation can be mitigated by gene modulation.
Purpose of Study
- To develop a nanoparticle system for in vivo gene silencing.
- To explore therapeutic formulations for diseases requiring gene modulation.
- To demonstrate the versatility of the nanoparticle platform.
Methods Used
- Assembling a Teflon etch cell with a silicon wafer.
- Using hydrofluoric acid for etching the silicon.
- Applying alternating current with specific parameters for nanoparticle formation.
- Rinsing the etch cell to prepare for further use.
Main Results
- Successful synthesis of fusogenic porous silicon nanoparticles.
- High efficiency in delivering siRNA for gene silencing.
- Potential for therapeutic applications in various diseases.
- Demonstrated ability to terminate chronic inflammation in macrophages.
Conclusions
- Fusogenic nanoparticles are promising for gene therapy.
- Customizable delivery systems can target specific diseases.
- Further research is warranted to explore additional applications.
Frequently Asked Questions
Executive Industry Relevance
Fusogenic porous silicon nanoparticles (F-pSiNPs) represent a modular platform for oligonucleotide delivery, enabling gene silencing with high efficiency and bypassing endocytic uptake barriers. This system supports rapid target validation and mechanistic de-risking in gene therapy discovery pipelines, with direct implications for portfolio expansion into infectious, oncologic, and immunologic indications. The approach enhances predictive confidence at the early discovery and preclinical inflection points by enabling precise, tunable delivery of nucleic acid payloads.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables direct interrogation of gene function via efficient in vivo gene silencing.
- Supports mechanistic de-risking by facilitating targeted modulation of disease-relevant pathways.
- Provides a flexible platform for rapid exchange of targeting peptides and oligonucleotide payloads.
- Improves predictive confidence for target selection and validation decisions.
Screening & Assay Development
- Delivers standardized, size-uniform nanoparticles characterized by dynamic light scattering for reproducible assays.
- Facilitates quantitative assessment of cellular uptake and fusion using confocal microscopy and fluorescent labeling.
- Enables scalable preparation of validated delivery vehicles for downstream screening workflows.
- Supports reliable evaluation of oligonucleotide efficacy in cell-based and in vivo models.
Translational & Preclinical Research
- Aligns with disease-relevant models, including infectious and inflammatory disease systems.
- Maintains translational continuity by supporting in vivo gene modulation in preclinical studies.
- Reduces biological risk by enabling functional validation of therapeutic hypotheses in relevant animal models.
- Facilitates risk-adjusted advancement of gene therapy candidates.
Pipeline & Workflow Integration
The F-pSiNP platform integrates from early discovery through preclinical validation, supporting hypothesis testing, lead identification, and translational research.
- Discovery Biology: Provides a robust tool for isolating gene function and clarifying pathway roles via targeted oligonucleotide delivery.
- Screening: Offers reproducible, quantitative outputs for nanoparticle size, charge, and fusion efficiency.
- Analytics: Enables direct measurement of cellular uptake, membrane fusion, and gene silencing outcomes.
- Translational Research: Supports continuity from in vitro validation to in vivo efficacy in disease-relevant models.
- Enterprise Reuse: Functions as a modular delivery system adaptable to diverse oligonucleotide and targeting peptide combinations.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in gene therapy R&D.
- Operational Value: Standardizes nanoparticle synthesis and characterization for reproducible results.
- Strategic Value: Enables informed go/no-go decisions and capital-efficient portfolio progression.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of gene modulation strategies.
Implementation Considerations
- Requires expertise in nanoparticle synthesis, surface functionalization, and analytical characterization.
- Demands access to dynamic light scattering, confocal microscopy, and extrusion instrumentation.
- Necessitates cross-team standardization of nanoparticle preparation and quality control protocols.
- Adaptable to various oligonucleotide payloads and targeting peptides for different disease models.
- Aggregation risk and storage stability must be managed to maintain functional performance.
Biopharma FAQs
Chapters in this video
0:04
Title
0:42
Synthesis of Porous Silicon Nanoparticles (pSiNPs)
3:12
Preparation of Fusogenic Lipid Film and Loading of siRNA in pSiNPs
4:20
Coating siRNA-loaded pSiNPs with Fusogenic Lipids
5:42
Conjugation of Targeting Peptides
6:45
Results: Characterization of Fusogenic Silicon Nanoparticles for Oligonucleotide Delivery
8:16
Conclusion
