Non-viral Gene Therapy - Intracellular Delivery: Fundamentals and Applications - page 659

attributed to the physical stabilization of the nanoplexes and the increasing of
buffering capacity, respectively. It is noteworthy that modified silica nanoparticles
also exhibited promise in in vivo studies. Prasad et al. showed that sterotaxic injec-
tion of functionalized silica nanoplexes gave transfection efficiency that equaled or
even exceeded that obtained with herpes simplex virus l vectors and showed less
tissue damage (Bharali et al. 2005 ).
Luo et al. noticed that unmodified silica nanoparticles could serve as mediators
for the uptake of DNA into cells by adsorbing on the cell surface (Luo et al. 2004 ).
As a result, b -galactosidase gene expression was enhanced by up to 750%. In addi-
tion, large silica particles were found to enhance gene expression more efficiently
than small ones, because of the faster settling of the larger particles onto the cell
surface. The co-precipitation of other inorganic or polymeric particles together with
DNA on cell surfaces also showed effective transfection, indicating that the chemical
composition of the nanoparticles is not a significant factor dominating the transgene
activity, which means this enhanced DNA uptake is kind of a “mechanical” effect.

5.5 Quantum Dots

Quantum dots (QDs) are luminescent semiconductor nanocrystals with typical diam-
eters of a few nanometers which comprise periodic groups of II-IV (e.g. CdSe and
CdTe) or III-V (e.g. InP and InAs) semiconductor materials (Alivisatos et al. 2005 ; Yin
and Alivisatos 2005 ; De et al. 2008 ). For these nanocrystals with all three dimensions
less than the Bohr exciton radius (typically a few nanometers), their energy levels are
quantized, which means the spacing of their energy levels can be controlled by the
crystal size (Nirmal and Brus 1999 ; Poznyak et al. 2005 ). This effect endowed QDs
superior properties over other organic fluorophores, such as narrow, symmetric and
size-tunable emission spectra, and broad excitation spectra. Another benefit of QDs
over organic fluorophores is their stronger fluorescence (~10-100 times brighter) and
higher fluorescence stability against photobleaching (~100-1,000 times more stable),
which is very important to the long-term monitoring of intermolecular and intramo-
lecular interactions in live cells and organisms (Salgueiriño-Maceira et al. 2006 ;
Resch-Genger et al. 2008 ). There are different routes devised for the preparation of
QDs, the predominant one is to coat a CdSe core with ZnS layer to obtain the best
crystalline quality and monodispersity. The reason for introducing ZnS is to reduce
toxicity by preventing the CdSe from leaching out to the surrounding solutions, and
also enhances the photoluminescence yield (Pinaud et al. 2006 ; Norris et al. 2008 ;
Smith et al. 2008 ). However, due to the fact that ZnS-coated QDs are not soluble in
aqueous milieu, which is the nature of the biological environment, altering the QDs
surface properties from hydrophobic to hydrophilic is quite necessary for biological
applications (Rogach et al. 2000 ; Gaponik et al. 2002 ). Furthermore, the inherent toxicity
of II-IV and III-V semiconductor QDs is a serious issue for in vivo applications. They
must rely on conjugation with biological molecules such as aptamers (Chu et al. 2006 ),
antibodies (Gao et al. 2004 ), peptides (Cai et al. 2006 ), ODNs (Zhang et al. 2005 ), and
small molecule ligands (Lidke et al. 2004 ) to obtain biological affinity.