The production of gold nanostructures such as nanoplates,
nanoshells, and nanorods with plasmon resonance frequencies in
the near infrared (nIR) region of the electromagnetic spectrum is
currently an area of growing research focus [1–4]. The importance
of the nIR region (650–900 nm) in medicine is due to the high
transmission and low absorption of light by native tissue components,
such as water and hemoglobin [6–8]. Thus, nIR light has
minimal interference with tissue and interacts strongly with exogenous
materials that absorb nIR light. This enables targeted drug
delivery and biosensing, as well as combined therapeutic and
imaging (theranostics) capabilities such as nIR imaging and photothermal
treatment in situ [7,9–14].
To date, a number of methods have been employed to synthesize
gold nanoparticles (GNPs), including nanoshells [15–19],
nanorods [20–27], nanocages [28–30], nanostars [31–34], and
nanoplates [35–51] that absorb in the nIR spectral region. Although
these methods produce nIR-GNPs, they are typically seed mediated
syntheses that require multiple steps, use toxic agents, difficult to
remove surfactants (i.e. CTAB) or require laborious purification
steps that significantly reduce product yield. However, of the above
mentioned techniques, one of the most promising approaches to
synthesizing nIR particles is through the reaction of chloroauric
acid (HAuCl4) with a sulfur-containing reducing agent (i.e. sodium
sulfide or sodium thiosulfate) using either a 1- or 2-step process
[49,50,52–58]. The reaction with either of the sulfur reagents can
be performed at room temperature and produce similar products.
Sodium sulfide (Na2S) is typically ‘‘aged’’ for several days in
solution, prior to the reaction, during which time sodium thiosulfate
(Na2S2O3) and potentially other oxidized sulfur species(S2O62, SO42, or SO3
2) are generated [54]. The products of this
reaction are separated into two major classes: colloidal gold nanoparticles
(2–10 nm diameter) with a plasmon resonance peak at
530 nm, and a nIR-absorbing fraction (nIR-GNP) with a resonance
wavelength that can vary from 650 to 2000 nm depending on the
synthesis conditions. The particle sizes and geometries reported
in the literature for the nIR-absorbing fraction vary widely and
are typically polydisperse, with spheroids, triangular nanoplates,
nanorods, and various other polyhedra ranging in size from 30 to
100 nm [52,55,56]. While the identity of the spheroidal particles
in the nIR fraction is the subject of considerable debate (colloidal
aggregates vs. gold/gold sulfide nanoshells), the present work is
primarily concerned with increasing the yield of the triangular
nanoplates, which show intense absorption in the nIR range
[7,49,51–55,59–61]. In addition to the intense nIR absorbance of
gold nanoplates, the plasmon resonance frequency is dependent
on the geometric properties of the plates (i.e. edge length, plate
thickness, and vertex shape) and is therefore tunable depending
on the reaction conditions used for synthesis [42,50,62].
Unfortunately, uptake of some non-therapeutic (non-nIR) particles
has the potential to lead to increased oxidative stress and
immune response [63–65]. For therapeutic applications, the colloidal
gold fraction can be considered a contaminant and is typically
separated from the nIR-absorbing fraction through multiple rounds
of centrifugation [7]. While effective, this purification process
results in a significant loss in the yield of therapeutic particles that
remain within the supernatant or experience irreversible
aggregation.
The ratio of absorbances (optical densities, OD) of the nIR resonance
maximum (AbsnIR) to the absorbance maximum for colloidal
gold (Abs530nm), herein defined as the quality ratio (QR = AbsnIR/
Abs530nm), can be used to assess the purity of a particular batch
of particles in terms of nIR content. Typical ‘‘traditional’’ synthesis
processes have been shown to produce QRs ranging from 0.8 to 1.2
[7,13,50,52,54]. However, after multiple rounds of centrifugation,
the QR has been shown to improve to between 1.5 and 2.0, respectively
[7,50].
As a result, significant room for improvement exists in the production
of nIR particles through the gold salt/sulfur reductant
route in terms of maximizing the yield of the nIR fraction, eliminating
colloidal contaminant in the final product, improving the tunability
of the nIR resonance frequency, and improving the
reproducibility of the morphologies of the nIR-GNP. Therefore,
the purpose of this work is to report on a new one-pot synthesis
methodology, called DiaSynth, which uses a regenerated cellulose
dialysis membrane as a reaction vessel to react HAuCl4 with Na2S2-
O3 to reproducibly synthesize nIR-GNPs in high yield without additional
purification processes. This self-assembly process also
enables in situ coating of nanoparticles and auxiliary utilization
of the dialysis membrane as an effective tool to separate the coated
product from the excess coating molecules.