“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics
Plasmonic Nanoparticles Application in Biosensor and Bioimaging 161
work in 1973^41 was enabled controlling over AuNPs size (16–147 nm)
by varying the feed ratio of gold salt to sodium citrate. Further studies
show reduction of HAuCl 4 by sodium citrate,^42 following a kinetically
controlled seeded growth strategy, resulting in monodisperse citrate
stabilized AuNPs with a uniform quasispherical shape of up to ∼ 200
nm and a narrow size distribution. This method proceeds via four
overlapping steps: nucleation, aggregation of nuclei, slow isotropic
growth via reduction and/or coalescence/Ostwald ripening, and
rapid consumption of the gold precursor.^43 Mechanistically, gold
reduction occurs through a concerted redox reaction, whereby citrate
is both chemically oxidized by chloroauric acid and thermally oxi
dized by heating to form dicarboxyacetone (DCA).44–46 Electrons
from DCA serve to reduce AuCl 3 to AuCl, which is believed to form
a bidentate complex with DCA. Particle nuclei forms via a dispropor
tionation reaction, where AuCl complexes combine to form zero
valent gold atoms and an AuCl 3 complex. Then, the inhibition of any
secondary nucleation during homogeneous growth was complete by
adjusting the reaction conditions: temperature, gold precursor to seed
particle concentration, and pH.46,47
A twophase synthetic strategy, (the Brust–Schiffrin method),
which utilizes strong thiol — gold interactions to protect AuNPs with
thiol ligands, was achieved by Brust and Schiffrin.^48 Due to the strong
thiol–gold interaction, these AuNPs can be repeatedly isolated and
redissolved in common organic solvents without irreversible aggrega
tion or decomposition, and they can be easily handled and functional
ized just as stable organic and molecular compounds. In this method,
AuCl 4 − is transferred from aqueous phase to toluene using the sur
factant tetraoctylammonium bromide (TOAB) and reduced by
sodium borohydride (NaBH 4 ) in the presence of dodecanethiol. On
addition of NaBH 4 , a quick color change from orange to deep brown
takes place in organic phase. The AuNPs are generated in toluene
with controlled diameters in the range 1.5−5 nm. Various reaction
conditions, such as gold/thiol ratio, temperature, and reduction rate,
can be used to tune the particle size.^28 For example, larger thiol/gold
mole ratios give smaller average core sizes, and fast reductant addition
and cooled solutions produced smaller, more monodisperse particles.
