Functional Mesoporous Silica Nanoparticles with a Core-Shell Structure for Controllable Drug Delivery - Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery - page 72

To date, a variety of stimuli-responsive controlled drug delivery systems
based on functional mesoporous silica nanoparticles with mesoporous silica
cores and functional shells have been developed (Lai et al. 2003; Casasús
et al. 2008; Hong et al. 2008; Patel et al. 2008; Du et al. 2009; Gao et al. 2009;
Vivero-Escoto et al. 2009; Bernardos et al. 2010; Meng et al. 2010; Sun et al.
2010; Xhen, Zheng, et al. 2010; Chen, Chen, Fang, et al. 2011; Coll et al. 2011;
Gan et al. 2011; Ma et al. 2012). One strategy is to design functional meso-
porous silica nanoparticles by coating mesoporous silica nanoparticles
with stimuli-responsive polymer layers, biomolecules, or polyelectrolyte
multilayers to cap the mesopore channels, such as poly( N -isopropylacryl-
amide) (PNIPAAm), poly(acrylic acid) (PAA), N-(3-aminopropyl) methacryl-
amide hydrochloride (APMA), poly(2-(diethylamino)ethyl methacrylate)
(PDEAEMA), and poly(methacrylic acid- co -vinyl triethoxylsilane) (PMV)
(Hong et al. 2008; Gao et al. 2009; Sun et al. 2010; Xhen, Zheng, et al. 2010).
Hong et al. (2008) reported a smart core-shell nanostructure with a meso-
porous silica core and a thermoresponsive PNIPAAm nanoshell via surface
reversible addition-fragmentation chain transfer polymerization. PNIPAAm
nanoshell can be reversibly switched between open and closed states by the
change of temperature, which induce the controlled loading and release of
drugs from the core-shell mesoporous silica nanoparticles.
Another popular strategy is to design various “gatekeepers” to cap the
mesopore outlets of mesoporous silica nanoparticles, such as nanoparticles
and supramolecules (Lai et al. 2003; Casasús et al. 2008; Patel et al. 2008; Du et
al. 2009; Vivero-Escoto et al. 2009; Bernardos et al. 2010; Meng et al. 2010; Coll
et al. 2011; Gan et al. 2011). Using nanoparticles as gatekeepers, solid nanopar-
ticles were chemically attached on the pore outlets of modified mesoporous
silica and could be removable with various external stimuli to destroy the
chemical bonds, such as pH, redox potential, and temperature (Lai et al.
2003; Vivero-Escoto et al. 2009; Gan et al. 2011). For example, Lai et al. (2003)
reported a CdS nanoparticles capped MCM-41 mesoporous silica nanopar-
ticle redox-responsive controlled drug release system. Here, CdS nanocrys-
tals are capped on the mesopore outlets via the disulfide linkages, and the
disulfide linkages are chemically labile in nature and can be cleaved with
various disulfide-reducing agents, such as dithiothreitol (DTT) and mercap-
toethanol (ME). Hence, the release of the CdS nanoparticle caps from the
drug-loaded mesoporous silica nanoparticles can be regulated by introduc-
ing various amounts of release triggers. A CdS-capped MCM-41 controlled
drug release system exhibits less than 1.0% of drug release over a period of
12 h, suggesting a good capping efficiency of the CdS nanoparticles. The
addition of DTT disulfide-reducing molecules to the aqueous suspension of
CdS-capped mesoporous silica nanospheres triggered a rapid release of the
mesopore-entrapped drug, reaching 85% within 24 h, indicating a stimuli-
responsive controlled drug release manner for this system.
Macrocyclic organic molecule gatekeepers, a type of supramolecular gate-
keeper, can also be disassembled by external stimuli to release the trapped