Biomedical Engineering Reference
In-Depth Information
(IPPL). Then, PMAC-O, the allyl epoxidation product of PMAC, was further
modified by PEIx with low molecular weight (x 5 423,800, or 1,800). In vitro
experiments demonstrated that the PAMC-g-PEIx showed much lower
cytotoxicity and enhanced transfection efficiency in comparison with 25 kDa
PEI in 293T cells. The biodegradability of PMAC-g-PEIx can facilitate the
efficient release of pDNA from polyplexes and reduce cell cytotoxicity. They
further synthesized biodegradable polycations based on polycarbonates with
1800 Da PEI as gene vectors (Scheme 4.17B).
121
The resulting copolymers with
different compositions [P(MAC-co-DTCx)] underwent additional allyl epox-
idation and were thereby grafted by LMW PEI (1800 Da). Despite a slightly
lower DNA binding ability, the PEI-grafted polycarbonates, especially
P(MAC-co-DTC45.4)-g-PEI, presented apparently low cytotoxicity and much
higher gene transfection efficiency in comparison with 25 kDa PEI in 293T
cells. Moreover, preincubation of P(MAC-co-DTC6.7)-g-PEI showed a rapidly
weakening DNA binding capacity, while a suitable degradation rate of vectors
could facilitate the efficient release of pDNA from polyplexes after cellular
uptake and also reduce cell cytotoxicity.
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4.6.6 Nanoparticles
Nanoparticles also have been developed and employed as nonviral gene
vectors, including gold nanoparticles, silica nanoparticles, carbon nanotubes,
lipid-based nanoparticles, quantum dots, and polymeric hydrogels. Compared
to cationic carriers, nanoparticles are inert and exhibit less cytotoxicity;
compared to liposomes, nanoparticles are more stable with respect to physical
stresses.
Various
surface
modifications
have
been
used
to
improve
the
transfection efficiency of nanoparticles.
Gold nanoparticles (GNPs) are bioinert and nontoxic, and provide
attractive scaffolds for gene delivery vectors. GNPs of small size provide a
high surface-to-volume ratio, maximizing the grafting density of target
molecules, which allows further tuning of the surface charge and hydro-
phobicity. Various modifications to the surface of GNPs have been
investigated to improve the transfection efficiency. Hu et al. synthesized a
series of LMW PEI (800 Da)-conjugated gold nanoparticles, which showed 60-
fold higher transfection efficiency than that of PEI 25 kDa in 10% serum
medium.
122
Recently, Shan et al. developed dendrimer-entrapped gold
nanoparticles (Au DENPs).
123
The transfection efficiency of Au DENPs was
significantly higher than that of G5 PAMAM dendrimers without AuNPs
entrapped. The higher gene transfection efficiency of Au DENPs is primarily
due to the fact that the entrapment of AuNPs helps preserve the 3D spherical
morphology of the dendrimers, allowing for more efficient interaction between
dendrimers and DNA.
Silica nanotubes (SNTs) have become a promising material in biomedical
applications, owing to their unique properties. Biocompatibility and facile
modification through well-known silane chemistry make SNTs even more
