Stem cell-based regenerative medicine holds exceptional therapeutic potential and hence the
development of efficient techniques to enhance control over the rate of differentiation has been the
focus of active research. One of the strategies to achieve this involves delivering siRNA into stem cells
and exploiting the RNA interference (RNAi) mechanism. Transport of siRNA across the cell membrane
is a challenge due to its anionic property, especially in primary human cells and stem cells.
Moreover, naked siRNA incites immune responses, may cause off-target effects, exhibits low stability
and is easily degraded by endonucleases in the bloodstream. Although siRNA delivery using viral vectors
and electroporation has been used in stem cells, these methods demonstrate low transfection efficiency,
cytotoxicity, immunogenicity, events of integration and may involve laborious customization.
With the advent of nanotechnology, nanocarriers which act as novel gene delivery vehicles designed to
overcome the problems associated with safety and practicality are being developed. The various nanomaterials
that are currently being explored and discussed in this review include liposomes, carbon
nanotubes, quantum dots, protein and peptide nanocarriers, magnetic nanoparticles, polymeric nanoparticles,
etc. These nanodelivery agents exhibit advantages such as low immunogenic response, biocompatibility,
design flexibility allowing for surface modification and functionalization, and control over
the surface topography for achieving the desired rate of siRNA delivery and improved gene knockdown
efficiency. This review also includes discussion on siRNA co-delivery with imaging agents,
plasmid DNA, drugs etc. to achieve combined diagnostic and enhanced therapeutic functionality, both
for in vitro and in vivo applications.