Biomimetic one-pot synthesis of gold nanoclusters/nanoparticles for targeted tumor cellular dual-modality imaging
© Lin et al.; licensee Springer. 2013
Received: 14 February 2013
Accepted: 23 March 2013
Published: 15 April 2013
Biomimetic synthesis has become a promising green pathway to prepare nanomaterials. In this study, bovine serum albumin (BSA)-conjugated gold nanoclusters/nanoparticles were successfully synthesized in water at room temperature by a protein-directed, solution-phase, green synthetic method. The synthesized BSA-Au nanocomplexes have fluorescence emission (588 nm) of gold nanoclusters and surface plasmon resonance of gold nanoparticles. The BSA-Au nanocomplexes display non-cytotoxicity and excellent biocompatibility on MGC803 gastric cancer cells. After conjugation of folic acid molecules, the obtained BSA-Au nanocomplexes showed highly selective targeting for MGC803 cells and dual-modality dark-field and fluorescence imaging.
Fluorescent materials as prominent tools have been widely investigated and applied in many practical fields, including mineralogy, gemology, chemical sensors (fluorescence spectroscopy), fluorescent labeling, dyes, biological detectors, and, most commonly, fluorescent lamps [1–3]. To date, there are three main types of fluorescent materials: organic dyes, fluorescent proteins, and nanotech probes . Compared with existing organic dyes and fluorescent proteins, nanotech probes can offer signals that are several folds brighter and hundreds of times more stable [5, 6]. The range of substances of nanotech probes mainly includes carbon, semiconductors, and precious metals .
Carbon nanotubes, due to their natural photoluminescence in the tissue-penetrating near-infrared region, have been successfully explored as potential imaging tools . Recently, carbon dots as a relative newcomer have multicolor emission capabilities and non-toxic nature, which enable them to be engaged in a wide range of applications in the biomedical field . Unlike semiconductor nanomaterials or quantum dots (QDs), however, the fluorescent properties of carbon-based probes are harder to control . QDs (such as CdSe, CdTe, and PbTe) have received broad attention due to their unique optical and biochemical features. However, the release of Cd2+, Pb2+, or other heavy metal ions arouses cytotoxicity and is a potential environmental hazard, which limits the applications of QDs [9, 10].
More recently, precious metal nanoparticles (such as gold nanoclusters (AuNCs)) are highly attractive because of their high fluorescence, good photostability, non-toxicity, excellent biocompatibility, and solubility [11, 12]. Biomimetic synthesis has become a promising green pathway to prepare nanomaterials [13–16]. Ying’s group used the protein bovine serum albumin (BSA) as a scaffold to make AuNCs (<1 nm) with red emission (640 nm) via a simple, one-pot, solution-phase, green synthetic route within 12 h [17, 18]. Zhu et al. have successfully prepared AuNCs with near-infrared emission and Au@AgNCs with yellow emission using a BSA-assisted sonochemical approach . Therefore, organic fusion of the fluorescence emission of AuNCs and the surface plasmon resonance of gold nanoparticles (AuNPs) enables dual-modality dark-field and fluorescence imaging.
Herein, we reported a simple ‘one-pot’ synthesis of gold nanoclusters/nanoparticles by using chloroauric acid (HAuCl4·3H2O) along with hydrazine monohydrate (N2H4·H2O) as reducer in the presence of BSA under vigorous stirring. The synthesized AuNCs and AuNPs own fluorescence emission (588 nm) and surface plasmon resonance (500~700 nm), respectively. The BSA-Au nanocomplexes display non-cytotoxicity and excellent biocompatibility on MGC803 gastric cancer cells. After being conjugated with folic acid molecules, the BSA-Au nanocomplexes demonstrate various functions such as tumor targeting and dual-modality imaging.
In a typical experiment, aqueous HAuCl4 solution (5 mL, 50 mM) was added to BSA solution (10 mL, 3 mg/mL) with vigorous magnetic stirring at room temperature. Afterward, the mixed solution was vacuumized and kept static under nitrogen protection for 2 h. Then, 0.2 mL of N2H4·H2O was injected into the vacuumed solution under magnetic stirring. After reaction, the resulting mixed solution was aged under ambient conditions for 24 h.
Results and discussion
The X-ray photoelectron spectroscopy (XPS) spectrum (Figure 1d) shows the existence of C, N, O, and Au in the BSA-Au nanocomplexes. The peaks of C, N, and O elements are due to the presence of BSA. The inset spectrum of the Au 4f band confirms the presence of the Au element in the products. The FT-IR spectrum of the BSA-Au nanocomplex is similar to that of BSA (Additional file 1: Figure S2), which indicates that the BSA plays a direction role in the reaction progress.
BSA, a ubiquitous plasma protein with a molecular weight of 66,500 Da, is composed of 580 amino acid residues [23, 24]. Due to their wide hydrophobic, hydrophilic, anionic, and cationic properties, BSA has been extensively used as a model protein in many fields including drug delivery , biomimetic mineralization , nanomaterial synthesis [27, 28], surface modification and intermolecular interaction , etc. More recently, our group has successfully prepared a series of semiconductor chalcogenides with different sizes and morphologies in a solution of BSA at room temperature [10, 27, 30]. In this case, BSA plays multifunctional roles: (1) to direct the synthesis of Au nanocomplexes, (2) to stabilize the Au nanocomplexes, (3) to improve the biocompatibility of Au nanocomplexes, and (4) to provide bioactive functionalities into these nanocomplexes for further biological interactions or coupling.
In summary, biocompatible BSA-Au nanocomplexes were successfully synthesized in water at room temperature by a protein-directed, solution-phase, green synthesis method. The as-prepared BSA-Au nanocomplexes showed highly selective targeting and dark-field and fluorescence imaging on MGC803 cells. It may have great potential in applications such as tumor targeting imaging, drug delivery, and ultrasensitive detection. The current study provides further evidence of the biomimetic fabrication of functional materials and exemplifies the interactions between proteins and metal nanomaterials in an attempt to create novel bioconjugated composites.
This work is supported by the National Key Basic Research Program (973 Project) (2010CB933901 and 2011CB933100), National 863 Hi-tech Project of China (no. F2007AA022004), Important National Science & Technology Specific Projects (2009ZX10004-311), National Natural Scientific Fund (81225010, 1101169, 31100717, 81272987, 51102258), New Century Excellent Talent of Ministry of Education of China (NCET-08-0350), and Zhejiang Provincial Natural Science Foundation of China (LY12H11011).
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