Biomedical Engineering Reference
In-Depth Information
genes or drugs, nanodimensional calcium orthophosphates provide
a protective environment that shields them from degradation while
providing a convenient pathway for cell membrane penetration and
controlled release of the genes or drugs [436]. The experimental
results proved that nanodimensional calcium orthophosphates
possessed a higher penetration rate into cell membranes and
their transfection efficiency could be 25-fold higher than that of
the micron-sized particles. Furthermore, due to the larger specific
surface areas, nanodimensional calcium orthophosphates can hold
larger load amounts of drugs than coarser particles. These results
indicate the potential of nano-sized calcium orthophosphates in
gene delivery and as drug carriers [436, 616-619]. Furthermore,
nanodimensional calcium orthophosphates can be stably loaded
with radioisotopes [282, 620].
A transfer of functional foreign nucleic acids (DNA or RNA) into
nuclei of living cells (transfection) with the aim of repairing missing
cell function and to provide means to enhance or silence gene
expression is currently used extensively in the laboratory and is fast
becoming a therapeutic reality. As nucleic acids alone are unable to
penetrate the cell wall, efficient carriers are required [621, 622].
Nanodimensional calcium orthophosphates can be represented as
a unique class of the non-viral vectors, which can serve as efficient
and alternative DNA carriers for targeted delivery of genes [256,
610, 623-635] and cells [485, 636-642]. The standard transfection
method using calcium orthophosphates, first introduced by Graham
and van der Eb in 1973 [641], is still used in biochemistry. It involves
a straightforward
precipitation of calcium orthophosphate/
DNA aggregates. Interestingly, but the transfection efficiency of
nanodimensional calcium orthophosphates were found to depend
on Ca/P ionic ratio: namely, calcium orthophosphates with Ca/P =
1.30 ratio exhibited a fourfold increase in the transfection efficiency
over the ones with Ca/P = 1.65 ratio composition [256]. This data
emphasize the importance of understanding the interaction between
calcium orthophosphates and DNA to optimize the DNA uptake
and its channeling to the nucleus of the cell. Besides, it has been
demonstrated that surface modified particles of nano-sized calcium
orthophosphates can be used
in situ
to target genes specifically
to a liver [643]. Attachment of galactose moiety onto the particle
surface has increased the targetability of the nano-sized particles.
Furthermore, this surface modification makes it possible for site-
in vivo
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