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Triggered RNAi Therapy Using Metal Inorganic Nanovectors
Eva Villar-Alvarez, Baltazar H Leal, Adriana Cambón
1Departamento de Cirugía Cardíaca, Complexo Hospitalario Universitario A Coruña , Instituto de Investigación Biomédica de A Coruña (INIBIC) , 15006 A Coruña , Spain.
Molecular Pharmaceutics
|June 13, 2019
Summary
New gold nanorod (GNR) carriers deliver small interfering RNA (siRNA) effectively for gene therapy. These non-toxic nanocarriers provide sustained gene silencing with enhanced activity based on siRNA layer count.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- Effective delivery of small interfering RNA (siRNA) is crucial for treating genetic diseases like Alzheimer's and cancer.
- Current siRNA delivery methods face challenges in stability and targeted release.
Purpose of the Study:
- To develop and analyze gold nanorod (GNR)-based platforms functionalized with polyelectrolyte layers as potential siRNA nanocarriers.
- To investigate the controlled release, stability, cytotoxicity, cellular uptake, and gene silencing efficiency of these nanocarriers.
Main Methods:
- Layer-by-layer assembly of polyelectrolyte layers (PSS, PLL, siRNA, hyaluronic acid) onto GNRs.
- Characterization of nanocarrier properties including cargo release, colloidal stability, cytotoxicity, cellular internalization, and gene knockdown activity.
Main Results:
- Successfully developed GNR-based nanocarriers with enhanced colloidal stability and targeting ability.
- Demonstrated protease-assisted and light-triggered release mechanisms for controlled siRNA delivery.
- Achieved efficient, non-toxic cellular uptake and sustained gene knockdown (up to 93% for 72 hours).
- Observed enhanced silencing activity with an increased number of siRNA layers.
Conclusions:
- GNR-based nanocarriers offer a promising, non-toxic platform for effective and sustained siRNA delivery.
- The developed nanocarriers enable on-demand oligonucleotide release and efficient gene silencing for therapeutic applications.
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