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
Published in:Asian journal of pharmceutical sciences 2018-11, Vol.13 (6), p.592-599
Main Authors: Slita, Anna, Egorova, Anna, Casals, Eudald, Kiselev, Anton, Rosenholm, Jessica M.
Format: Article
Language:English
Subjects:
Gene therapy
Mesoporous silica nanoparticles
Nanocarriers
Research Paper
siRNA delivery
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
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. [Display omitted] Modified mesoporous silica nanoparticles (MSNs) where the pores are surface functionalized with polyethylene imine (PEI) and linkers containing intracellularly cleavable SS bonds, and a particle surface covered with pre-polymerized PEI were evaluated for their transfection efficiency in MDA-MB 231 breast cancer cells stably expressing GFP. PEI-coated siRNA/MSN complexes provide significantly more effective delivery of siRNAs compared to unmodified MSNs.
ISSN:1818-0876
2221-285X
DOI:10.1016/j.ajps.2018.01.006