The surface chemistry of near-infrared resonant gold nanotriangles obtained via thiosulfate synthesis

Highlights

• One-step synthesis using thiosulfate yields gold nanotriangles with NIR absorbance.

• Dimensions and properties of nanotriangles are adequate for photothermal therapies.

• Nanotriangle surface covered by reduced sulfur species.

• S-capped gold nanotriangles do not show toxic effect on fibroblast cells.

Abstract

Gold nanoparticles with NIR absorption are promising for photothermal therapy applications. Different syntheses have been proposed and, among them, that based on the reduction of Au(III) with thiosulfate is important because it yields gold nanotriangles (AuNTs) with strong absorption in the near-infrared region. It has been previously reported by others that the nanoparticle surface is covered by relatively weak adsorbed S species (mostly sulfate), which would render the surface easy to functionalize in order to improve biocompatibility and therapeutic effects. In this work we have used XPS, XANES, UV–vis–NIR spectroscopy, HRTEM and AFM to demonstrate that, in contrast to the previous reports, these AuNTs are covered by strongly adsorbed sulfur species (sulfide and polysulfide). A reaction pathway is proposed to explain the presence of reduced sulfur species and the absence of adsorbed sulfates and thiosulfates. Preliminary cytotoxicity assays show that the S-capped AuNTs do not show a deleterious effect for Au concentrations larger than those needed for in vivo photothermal treatments.

Introduction

Plasmonic gold nanoparticles (AuNPs) are of utmost interest in nanoscience due to their singular physico-chemical properties, many of them related to their localized surface plasmon resonance (LSPR), and play a key role for many nanotechnological applications such as sensing, electronic, optical devices, medical treatments and diagnostics [1], [2], [3], [4], [5]. This is even more so because of their chemical stability in different media and owing to the fact that they can be tailored in size and shape and post-functionalized to tune their surface properties and to immobilize different species of interest [1], [6].

In recent years much effort has been done to improve the synthesis of gold nanotriangles (AuNTs) because of the advantages related to their high anisotropy and the energy of its LSPR in the NIR region [7], [8], [9], [10]. The optical and electrical properties of AuNTs are not only of interest in the field of basic plasmonics but also for their use as building blocks, metamaterials, templates and device components in sensors, as well as for nanomedical applications [11], [12], [13]. AuNTs are a promising alternative to gold nanorods and nanoshells for plasmonic photothermal therapies [11].

Many different protocols have been proposed, including seeded-mediated syntheses in the presence of cationic surfactants (like CTAB and CTAC), some with halide and/or Ag⁺ ions [8], [9], [14], syntheses with aminoacids as reductants [15], as well as with different natural products [16], [17], [18] and vesicles [19], [20]. Many of these have a low AuNT yield and give a mixture of nanoparticles of different shapes, making necessary a post-synthesis separation step. Also, it is still a challenge to produce AuNTs that absorb beyond 750 nm: this difficulty mostly resides in the fact that AuNTs with side length < 100 nm (the optimal size range for a successful targeting in cancer therapies due to the leaky vasculature) need to be thinner than 15 nm in order to absorb at such low energies [21].

An interesting strategy to overcome this is the use of sulfur compounds as reducing agents of Au(III) ions in aqueous solutions. Sulfide and thiosulfate have been both used to obtain truncated AuNTs with intense absorption in the so-called NIR-I biological window (around 800 nm) [22], [23], [24], [25], [26], [27]. However, due to the presence of spherical AuNPs in addition to the AuNTs, there has been some controversy about the nanoparticles responsible for NIR absorbance [28], [29], [30], [31], [32]. Indeed, only recently it has been possible to thoroughly understand the optical and chemical properties of the AuNPs synthesized with sulfide, a fact that has somehow limited their applications [21], [33].

Of the two syntheses, that with thiosulfate has attracted greater interest because it is easier to achieve, has a larger yield of AuNTs compared to the case of sulfide and because it has been suggested that the nanostructures surface is covered by relatively weak adsorbed species that could be easily removed by straightforward ligand exchange processes [24], [27]. In fact, the chemical reaction proposed by some authors involves the reduction of Au(III) to Au(0) by the thiosulfate ions that in turn oxidize to sulfates, which do not adsorb as strongly as other S species on gold surfaces [24], [27]. However, the chemistry of thiosulfate, especially in acidic media, exhibits a great complexity, opening the possibility for alternative reaction pathways that can lead to a completely different chemistry. Indeed, it is widely accepted that thiosulfate decomposes in acidic media resulting in elemental sulfur, sulfur dioxide, hydrogen sulfide and polysulfanes, among other species [34].

The surface chemistry of thiosulfate on metallic gold also reveals a great complexity, and different adsorbed S species have been detected. Indeed, gold sulfide, S₈, pyritic S₂²⁻ and tetrathionate-like species have been detected by XPS for polished gold in thiosulfate solutions [35]. Also, STM studies show that the initial immersion of Au(1 1 1) substrates in thiosulfate solutions in alkaline media results in the formation of ordered adlayers of thiosulfate ions that can be reduced to yield sulfide species that adsorb as monomeric S [36]. Moreover, it is well-known that nanoparticles are more reactive than planar surfaces due to the large number of defects on their surface [37], [38], [39].

This opens new questions about the chemistry involved in the thiosulfate synthesis of AuNPs, not only concerning their bulk composition but also regarding the surface species present, especially if they are to be used for biomedical purposes [40], [41], [42]. In this work we present a thorough physico-chemical study of the synthesis of AuNTs resulting from the reaction of Au(III) with thiosulfate. Our results show that the AuNPs are covered by several strongly adsorbed reduced sulfur species, similar to those found when sulfide is used as the reductant [33]. This leads us to conclude that the thiosulfate synthesis proceeds by a mechanism that involves sulfide species as the reducing agent. Therefore, unlike what has been proposed by other authors, the route of thiosulfate oxidation to sulfate is not the only reducing pathway possible for Au(III) ion reduction [24], [27]. The presence of reduced S species on the surface of the AuNTs is most challenging and must be taken into account if the nanoparticles are designed for nanomedical applications. In fact, these species will affect postfunctionalization of the AuNTs and could have some deleterious effect on some cellular processes [43], [44]. Our preliminary in vitro studies show, however, that the S-capping does not show a detrimental effect on the studied fibroblast cell line.