Silica-Based Nanoparticles: Design and Properties - Advanced Fluorescence Reporters in Chemistry and Biology - page 231

environment [ 8 - 15 ]. Besides the biolabeling and biosensing, DDSNs can also be
functionalized for drug delivery. The multifunctional DDSNs which carry photo-
dynamic therapy agents or other anticancer drugs provide complete solutions from
diagnosis and therapy [ 16 - 20 ].
There has been a rapid development of DDSNs in last 10 years or so. Tan's
group reported a series of DDSNs using organic and inorganic fluorophores and
applied them as biolabeling materials for both imaging and sensing [ 8 , 10 - 12 ,
21 - 25 ]. The groups of Wiesner [ 6 , 13 , 14 , 26 ], Montalti [ 27 - 29 ], and Lakowicz
[ 30 - 34 ] among others [ 9 , 15 , 19 , 35 - 43 ], have designed highly intense DDSNs with
various structures and functions. These accomplishments have demonstrated the
great potential of DDSNs to be revolutionary fluorescent labeling materials in
bioanalysis.
In this chapter, the first section will focus on the designs of different structures of
DDSNs. The basic synthesis methods of pure silica nanoparticles will be briefly
summarized at the beginning. The general methods for doping dye molecules into a
silica matrix will then be covered followed by the introduction of several DDSN
designs. The second section will be a major focus of this chapter. Various advanta-
geous properties of DDSNs will be discussed. These discussions will involve
reaction kinetics, solubility, photostability, and fluorescence intensity including
quantum yield and lifetime, as well as toxicity. With the rapid development of
DDSNs, more features and functionalities of DDSNs are expected in the near
future.
2 Design of Dye-Doped Silica Nanoparticles
Generally, two common methods, the St¨ber method and the reverse microemul-
sion method are used for synthesis of silica nanoparticles. As derivatives of a
sol-gel process, both methods involve hydrolysis of a silicon alkoxide precursor
to form a hydroxysilicate followed by polycondensation of the hydroxysilicate to
form a silica nanoparticle [ 44 ].
Both the St ¨ ber method and the reverse microemulsion method can be used to
prepare DDSNs. In the process of synthesizing of silica nanoparticles, dye
molecules are added into the microemulsion either before or during the hydroly-
sis of the silicate precursor. However, some dye molecules cannot be doped
within silica nanoparticles. An association between dye molecules and the silica
matrix must exist to hold the dye molecules inside the silica matrix. A common
linking force is covalent binding, which provides a more stable linkage but
requires additional chemical reactions. Electrostatic interaction between the
negatively charged silica and positively charged dye molecules is frequently
employed as well. To design a DDSN, the firststepistoselectdyeswithdesired
wavelength and corresponding dye doping methods. Second, a suitable synthesis
method is to be chosen for the particle fabrication. Third, it is necessary to
optimize particle size, pore structure, surface groups, and dye density. In addition