Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 334

RES reticuloendothelial system

siRNA short-interfering RNA

TEOS tetraethoxysilane

1 Introduction

Chemistry at the nano-bio interface is one of the most promising challenges of the
2000s, as a more and more sophisticated set of tools can be used to take advantage
of the unique properties of nanomaterials. Indeed, their physical and chemical
properties deviate significantly from the bulk properties of such materials, and a
perfect control of chemistry allow to design a wide range of nanostructures of con-
trolled size, shape, dispersity and surface chemistry. The complexity of these struc-
tures can go from simple spheres to nanotubes or nanowires, going through
core-shell particles, hollow capsules, prisms, Janus particles, etc. Also their surface
could be differentially functionalized on their inner and outer surfaces, opening a
wide field for applications in drug delivery and medical therapy.
One of the first significant attempts to conjugate inorganic nanoparticles to
biological molecules came out in the 1990s, when semiconductor quantum dots
were coupled to antibodies in order to target them to specific biomolecules into the
cells (Bruchez et al. 1998 ). These experiments demonstrate the efficiency of
brightly luminescent quantum dots for intracellular imaging, that make these nano-
crystals probes to be considered as novel candidates that could be, in some cases,
more competitive than existing fluorophores. New strategies for delivery of short-
interfering RNA (siRNA) to cells using nanoparticles were also developed by coating
semiconductor quantum dots with proton-absorbing polymeric layers that allow the
nanoparticle and its siRNA cargo to perform the functions of cellular penetration,
endosomal release, carrier unpacking and intracellular transport (Yezhelyev et al.
2008 ). Other authors showed that a high packing density of siRNA on the surface
of gold particles inhibit its degradation by nucleases and promotes its uptake by
HeLa cells (Giljohann et al. 2009 ).
Among inorganic particles, silica colloids represent a very unique situation. First
their synthesis and further functionalization is rather simple and highly versatile, as
discussed in several reviews (Wang et al. 2008 ; Jin et al. 2009 ; Taylor-Pashow et al.
2010 ). Second, silica is usually considered as a non-toxic material, a property that
it shares with only a few other inorganic materials such as calcium phosphate,
calcium carbonate and iron oxides. It is therefore not surprising that silica nanopar-
ticles have been widely studied for biomedical applications: imaging, drug delivery,
ultra-trace detection, DNA/RNA delivery or therapy.
In particular, the evaluation of silica-based nanoparticles as drug carriers has
become very popular among the last 5 years or so (Slowing et al. 2008 ; Di Pasqua
et al. 2008 ; Rosenholm et al. 2010 ). Over this period, silica particles of increasing
complexity, in terms of structure, chemical composition and biological responses
have been designed. Such a complexity reflects the many requirements of drug