Gold nanomaterials as a new tool for bioanalytical applications of laser desorption ionization mass spectrometry

Nanomaterials have emerging importance in laser desorption ionization mass spectrometry (LDI–MS) with the ultimate objective being to overcome some of the most important limitations intrinsically related to the use of conventional organic matrices in matrix-assisted (MA) LDI–MS. This review provides a critical overview of the most recent literature on the use of gold nanomaterials as non-conventional desorption ionization promoters in LDI–MS, with particular emphasis on bioanalytical applications. Old seminal papers will also be discussed to provide a timeline of the most significant achievements in the field. Future prospects and research needs are also briefly discussed.     

Biological applications of gold nanoparticles

This critical review gives a short overview of the widespread use of gold nanoparticles in biology. We have identified four classes of applications in which gold nanoparticles have been used so far: labelling, delivering, heating, and sensing. For each of these applications the underlying mechanisms and concepts, the specific features of the gold nanoparticles needed for this application, as well as several examples are described (142 references).     

Bacterial spores as platforms for bioanalytical and biomedical applications

Genetically engineered bacteria-based sensing systems have been employed in a variety of analyses because of their selectivity, sensitivity, and ease of use. These systems, however, have found limited applications in the field because of the inability of bacteria to survive long term, especially under extreme environmental conditions. In nature, certain bacteria, such as those from Clostridium and Bacillus genera, when exposed to threatening environmental conditions are capable of cocooning themselves into a vegetative state known as spores. To overcome the aforementioned limitation of bacterial sensing systems, the use of microorganisms capable of sporulation has recently been proposed. The ability of spores to endow bacteria-based sensing systems with long lives, along with their ability to cycle between the vegetative spore state and the germinated living cell, contributes to their attractiveness as vehicles for cell-based biosensors. An additional application where spores have shown promise is in surface display systems. In that regard, spores expressing certain enzymes, proteins, or peptides on their surface have been presented as a stable, simple, and safe new tool for the biospecific recognition of target analytes, the biocatalytic production of chemicals, and the delivery of biomolecules of pharmaceutical relevance. This review focuses on the application of spores as a packaging method for whole-cell biosensors, surface display of recombinant proteins on spores for bioanalytical and biotechnological applications, and the use of spores as vehicles for vaccines and therapeutic agents.     

The flow-through silica as the matrix to immobilize gold nanoparticles for HPLC applications

In the present study, the flow-through silica, featured with hierarchical pores, i.e., tunable mesopores and penetrable macropores, was attempted as the chromatographic stationary phase matrix to immobilize gold nanoparticles (AuNPs). It was first modified by mercapto groups (named as SiO₂-SH), and then by AuNPs (named as SiO₂-S-Au). Thanks to the characteristic macropores, the column backpressure of SiO₂-S-Au was comparable to SiO₂-SH, which effectively overcame the difficulty of high column backpressure upon the nanoparticles were introduced to the chromatographic matrix. Both the reversed-phase and hydrophilic interaction liquid chromatographic performance were observed on these two columns but with different selectivities. Hydrophobic, hydrophilic, hydrogen bond and electrostatic interactions between the SiO₂-S-Au stationary phase and analytes could contribute to the retention. The SiO₂-S-Au column showed excellent aqueous compatibility by “Stop-flow” test with the relative standard deviations (RSD) of analyte’s k (capacity factor) values from 0.59% to 2.88%. The reproducibility of SiO₂-S-Au was acceptable with RSDs of analyte’s k values in the range of 3.13%-5.03%. In addition, compared with the SiO₂-SH column, the SiO₂-S-Au column had better separation performance and selectivity. The results demonstrated that the flow-through silica was a promising matrix for nanoparticles with low backpressure and different selectivities.     

Bioconjugated quantum dots as fluorescent probes for bioanalytical applications

Quantum dots (QDs) are inorganic semiconductor nanocrystals that have unique optoelectronic properties responsible for bringing together multidisciplinary research to impel their potential bioanalytical applications. In recent years, the many remarkable optical properties of QDs have been combined with the ability to make them increasingly biocompatible and specific to the target. With this great development, QDs hold particular promise as the next generation of fluorescent probes. This review describes the developments in functionalizing QDs making use of different bioconjugation and capping approaches. The progress offered by QDs is evidenced by examples on QD-based biosensing, biolabeling, and delivery of therapeutic agents. In the near future, QD technology still faces some challenges towards the envisioned broad bioanalytical purposes.      

Surface chemistry of gold nanoparticles for health-related applications

Functionalization of gold nanoparticles is crucial for the effective utilization of these materials in health-related applications. Health-related applications of gold nanoparticles rely on the physical and chemical reactions between molecules and gold nanoparticles. Surface chemistry can precisely control and tailor the surface properties of gold nanoparticles to meet the needs of applications. Gold nanoparticles have unique physical and chemical properties, and have been used in a broad range of applications from prophylaxis to diagnosis and treatment. The surface chemistry of gold nanoparticles plays a crucial role in all of these applications. This minireview summarizes these applications from the perspective of surface chemistry and explores how surface chemistry improves and imparts new properties to gold nanoparticles for these applications.

Functionalization of gold nanoparticles is crucial for the effective utilization of these materials in health-related applications.     

Dipyrromethane as a new organic reagent for the synthesis of gold nanoparticles: preparation and application

Condensation reaction of several ketones with pyrrole in the presence of ferric hydrogen sulfate as a green homogenous acidic catalyst furnished the corresponding pure dipyrromethanes in good yields. Gold nanoparticles were produced through reduction of HAuCl₄ with substituted dipyrromethanes as new reducing agents at room temperature with the exclusion of any capping agent or surfactant. Gold nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, XRD and UV–visible absorption spectroscopic measurements. It is proposed that in situ formed oxidative products of dipyrromethane, such as polydipyrromethane could serve effectively as a capping agent to preferably adsorb the {111} facets of gold crystals during the reduction process, which leads to the formation of gold nanoparticles.     

Robust ligand shells for biological applications of gold nanoparticles

An important point regarding the development of stable biofunctional nanoparticles for biomedical applications is their potential for aspecific interactions with the molecules of the biological environment. Here we report a new self-assembled ligand monolayer system for gold nanoparticles called Mix-matrices, formed by a mixture of HS-PEG and alcohol peptides (peptidols) molecules. Stability of the Mix-capped nanoparticles prepared in various conditions was assessed using tests of increasing stringency. The results highlight the importance of identifying a concentration of ligands sufficiently high to obtain a compact matrix when preparing nanoparticles and that the stability of capped nanoparticles in biological environments cannot be predicted solely on their resistance to electrolyte-induced aggregation. The Mix-capped nanoparticles are resistant to aggregation induced by electrolytes and to aspecific interactions with proteins and ligand exchange. In addition, Mix-matrices allow the easy introduction of a single recognition function per nanoparticle, allowing the specific and stoichiometric labeling of proteins with gold nanoparticles. Therefore, the Mix-matrices provide a useful tool for the development of nanoparticle-based quantitative bioanalytical and imaging techniques, as well as for therapeutic purposes, such as the specific targeting of cancerous cells for photothermal destruction.     

Preparation of sterically stabilized gold nanoparticles for plasmonic applications

Plasmonic nanoparticles such as those of gold or silver have been recently investigated as a possible way to improve light absorption in thin film solar cells. Here, a simple method for the preparation of spherical plasmonic gold nanoparticles in the form of a colloidal solution is presented. The nanoparticle diameter is controlled in the range from several nm to tens of nm depending on the synthesis parameters with the size dispersion down to 14 %. The synthesis is based on thermal decomposition and reduction of the chloroauric acid in the presence of a stabilizing capping agent (surfactant) that is very slowly injected into the hot solvent. The surfactant prevents uncontrolled nanoparticle aggregation during the growth process. The nanoparticle size and shape depend on the type of the stabilizing agent. Surfactants with different lengths of the hydrocarbon chains such as Z-octa-9-decenylamine (oleylamine) with AgNO₃ and polyvinylpyrrolidone with AgNO₃ were used for the steric stabilization. Hydrodynamic diameter of the gold nanoparticles in the colloidal solution was determined by dynamic light scattering while the size of the nanoparticle metallic core was found by small-angle X-ray scattering. The UV-VIS-NIR spectrophotometer measurements revealed a plasmon resonance absorption in the 500–600 nm range. Self-assembled nanoparticle arrays on a silicon substrate were prepared by drop casting followed by spontaneous evaporation of the solvent and by a modified Langmuir-Blodgett deposition. The degree of perfection of the self-assembled arrays was analyzed by scanning electron microscopy and grazing-incidence small-angle X-ray scattering. Homogeneous close-packed hexagonal ordering of the nanoparticles stretching over large areas was evidenced. These results document the viability of the proposed nanoparticle synthesis for the preparation of high-quality plasmonic templates for thin film solar cells with enhanced power conversion efficiency, surface enhanced Raman scattering, and other applications.     

Enzymeless determination of cholesterol using gold and silver nanoparticles as electrocatalysts

We present the results of synthesis and study of the electrocatalytic activity of gold and silver nanoparticles of different composition (individual metals, core–shell particles, nanoalloys, and particles synthesized electrochemically), immobilized on the surface of a glassy carbon electrode, with respect to cholesterol. A surfactant (cetyltrimethylammonium bromide) is selected to create an aqueous–organic emulsion of cholesterol. It is demonstrated that nanoparticles with a gold core and a silver shell with the regression equation of I = 1.4 × 10^–5 c _chol + 5.8 × 10^–5 (R ² = 0.97) and silver nanoparticles synthesized electrochemically with the regression equation of I = 1.0 × 10^–5 c _chol + 3.0 × 10^–4 (R ² = 0.95) possess optimal electrocatalytic characteristics.     

Simple spectrophotocolorimetric method for quantitative determination of gold in nanoparticles

A simple spectrophotocolorimetric method devoted to the measurement of gold content in nanoparticles (NPs) was developed. It includes two steps: (i) metal gold NPs (Au NPs) are oxidized into the AuCl₄⁻ anion using a 5 × 10⁻² M HCl-1.5 × 10⁻² M NaCl-7 × 10⁻⁴ M Br₂ solution, next (ii) AuCl₄⁻ concentration is measured using a spectrophotometric assay based on the reaction of AuCl₄⁻ with the cationic form of Rhodamine B to give a violet ion pair complex. This latter is extracted with diisopropyl ether and the absorbance of the organic complex is measured at 565 nm. The method is linear in the range 6-29 μM of AuCl₄⁻ with a limit of detection of 4.5 μM.The analytical method was optimized with respect of bromine excess to obtain complete Au NPs oxidation. The method was applied to two types of Au NPs currently under investigation: citrate-stabilized Au NPs and Au NPs capped with dihydrolipoic acid (Au@DHLA). Both the gold content of Au NPs and the concentration of NPs (using NP diameter measured by transmission electron microscopy) have been calculated.     

Synthesis and electrochemical applications of gold nanoparticles

This review covers recent advances in synthesis and electrochemical applications of gold nanoparticles (AuNPs). Described approaches include the synthesis of AuNPs via designing and choosing new protecting ligands; and applications in electrochemistry of AuNPs including AuNPs-based bioelectrochemical sensors, such as direct electrochemistry of redox-proteins, genosensors and immunosensors, and AuNPs as enhancing platform for electrocatalysis and electrochemical sensors.     

A new organic compound for the synthesis of gold nanoparticles

2,3,5,6-Tetrakis-(morpholinomethyl)hydroquinone (1) is used for the first time in the preparation of gold nanoparticles by the reduction of HAuCl₄ in water–methanol medium without using any capping agent. Compound 1 was prepared by Mannich-type aminomethylation of hydroquinone with morpholine. It is characterized by elemental analysis, FT-IR, UV–Vis and mass spectra and finally by single crystal X-ray diffraction. The ratio of HAuCl₄ and compound 1 played a vital role in controlling the shape and size of gold nanoparticles. The samples were characterized by Transmission Electron Microscopy (TEM), XRD, FT-IR, UV–Vis measurements. With the increasing amount of gold(III) solution with respect to compound 1, two different morphologies such as self-assembled and spherical gold nanoparticles have been observed. The results indicate that the morphology of gold nanoparticles with different sizes can be controlled by changing the concentrations of compound 1 and gold(III) solution.     

Self-assembled monolayers of organosulfur derivative on gold nanoparticles as electrochemical sensor for determination of isoprenaline

In this paper, the use of molecular self-assembled monolayers of 5-(1,3-dithiolan-2-eyl)-3-methyl banzen-1,2-diol (DMD) on gold nanoparticles was described (DMD-AuNPs). The redox properties of modified electrode at various scan rates were investigated by cyclic voltammetry. A pair of well-defined quasi-reversible redox peaks of DMD were obtained at the modified electrode. Dramatically enhanced electrocatalytic activity was exemplified at the DMD-AuNPs, as an electrochemical sensor to investigate the electro-oxidation of isoprenaline (IP). With this modified electrode, the oxidation potential of the IP was shifted about 235 mV toward a less positive potential value than that of an unmodified electrode. The values of electron transfer coefficients (α = 0.5), catalytic rate constant (ks = 9.2 s^?1) and diffusion coefficient (D = 8.9 × 10^?5 cm² s^?1) were calculated for IP. The response of catalytic current with IP concentration showed a linear relation in the range from 0.5 to 800 µM with a detection limit of 0.21 µM. Finally, this modified electrode was used for the determination of IP in IP injections.     

金纳米微粒作探针共振瑞利散射光谱法测定盐酸异丙嗪

在pH 1.8～3.0的酸性介质中,质子化的盐酸异丙嗪(PMZ)可与带负电荷的金纳米微粒依靠静电和疏水作用相互结合,导致共振瑞利散射(RRS)强度显著增强,其最大散射峰位于368 nm,并在284,440,498 nm处有明显的散射峰,在选定的测量波长下,盐酸异丙嗪在0.04～0.10μg/mL的浓度范围内与RRS强度成正比,该法具有高的灵敏度,其检出限为1.34 ng/mL。考察了体系的RRS光谱特征,研究了适宜的反应条件、影响因素,研究了共存物质的影响,据此建立了金纳米微粒作探针RRS法测定盐酸异丙嗪的新方法。     

Alkynylisocyanide gold mesogens as precursors of gold nanoparticles

Gold nanoparticles (Au NPs) have been synthesized using simple thermolysis, whether from the mesophase or from toluene solutions, of mesogenic alkynyl-isocyanide gold complexes [Au(C≡C-C(6)H(4)-C(m)H(2m+1))(C≡N-C(6)H(4)-O-C(n)H(2n+1))]. The thermal decomposition from the mesophase is much slower than from solution and produces a more heterogeneous size distribution of the nanoparticles. Working in toluene solution, the size of nanoparticles can be modulated from ~2 to ~20 nm by tuning the chain lengths of the ligands present in the precursor. Different experimental conditions have been analyzed to reveal the processes governing the formation of the gold nanoparticles. Experiments on the effect of adding ligands or bubbling oxygen support that the thermal decomposition is a bimolecular process that starts by decoordination of the isocyanide ligand, producing an oxidative coupling of the akynyl group to [R-C≡C-C≡C-R] and reduction of gold(I) to gold(0) as nanoparticles. The nanoparticles obtained behave as a catalyst in the oxidation of isocyanide (CNR) to isocyanate (OCNR), which in turn cooperates to catalyze the decomposition.     

金纳米粒子的表面修饰及生物应用进展

近年来纳米材料被广泛应用于生物医学、航空航天和精细化工等领域。构成纳米材料的纳米粒子具有小尺寸效应、表面效应和宏观量子隧道效应等性质。其中金纳米粒子由于其独特的荧光特性、良好的生物相容性和表面等离子共振等性质,被广大科研人员进行深入研究。例如,在生物医学领域,科研人员构建了一系列新型的金纳米比色传感器、光学探针及各类载药体系等。然而,目前金纳米粒子仍存在水分散性差、肾清除效率低和量子发射产率低等问题,限制了其广泛应用。因此,研究人员对金纳米粒子表面进行多样化修饰,从而能有效克服上述缺点。本文就目前主流配体表面修饰金纳米粒子的研究进展进行了详细总结,着重介绍了功能化金纳米粒子在生物成像、生物检测、生物治疗三方面的应用,最后对金纳米粒子的临床治疗机制的探索以及商业化的应用进行了展望,希望能为相关领域的研究者们提供新思路。