Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector draw...

Full description

Saved in:
Bibliographic Details
Main Authors: Anna Slita (Author), Anna Egorova (Author), Eudald Casals (Author), Anton Kiselev (Author), Jessica M. Rosenholm (Author)
Format: Book
Published: Elsevier, 2018-11-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery. Keywords: Gene therapy, Nanocarriers, siRNA delivery, Mesoporous silica nanoparticles
Item Description:1818-0876
10.1016/j.ajps.2018.01.006