Inorganic hybrid nanoparticles in cancer theranostics: understanding their combinations for better clinical translation

Drug resistance, tumor heterogeneity, and poor selectivity make cancer treatment with current modalities a challenging and complicated task. Careful planning of diagnosis and therapy is required to build new strategies for treatment and management of cancer. The amalgamation of therapeutics and diagnostics in a single nano agent, known as theranostics is now possible due to the emergence of nanotechnology. Theranostics offers opportunities for personalized medicine by real-time monitoring of drug accumulation and dynamic modification of treatment depending on individual patient needs. Thus potential to reform disease management is held by theranostic nanoparticles. Amongst other nanosystems, inorganic nanoparticles have been widely used for developing theranostic drug delivery systems due to their favorable intrinsic properties. The last decade has seen a surge in development of such theranostic nanoparticles in which various inorganic materials in different combinations have been engineered to maximize the output with respect to specific applications. For example, Fe₃O₄@Au nanoparticles were developed for MRI, hyperthermia and magnetically controlled drug delivery. Several such combinations leading to innovative theranostic applications and their underlying mechanisms have been highlighted in this review. A review of patents and clinical trials of inorganic theranostic nanoparticles is also presented through which we understood that clinical translation still remains in the nascent stage. Thus, it is necessary to find and understand reasons for lack of clinical translations. Therefore, we have discussed the challenges associated with bench-to-bed translation of such inorganic nanoparticles which show immense potential in vitro but fail to deliver in long run.     

Synthesis and Characterization of Gold Nanoparticle‐Functionalized Ordered Mesoporous Materials

We report the synthesis and characterization of three different ordered mesoporous materials, labeled MCM‐48, SBA‐155, and SBA‐16 type materials, which were functionalized with gold nanoparticles using three different strategies. The functionalization strategies can be categorized as (i) in situ growth of gold nanoparticles, (ii) template loading, and (iii) diffusion loading of prefabricated gold nanoparticles. Two different particle sizes were employed in the latter two strategies, 5 nm and 10 nm. For all mesoporous structures, functionalization strategies, and particle sizes attempted, the materials retained their long‐range order upon incorporation of nanoparticles. From the adsorption isotherms, incorporation of gold nanoparticles altered the pore structure of the mesoporous support of some of the SBA‐15 and SBA‐16 type materials, with the effect on incorporation on the pore structure being particle size dependent in most cases. The majority of gold nanoparticles were found to reside on the external surface of the materials regardless of substrate and functionalization strategy; however, for the in situ synthesis and the template loading strategies, a significant fraction of the particles was determined to reside within the pore system of the material. In situ growth resulted in the highest content of gold nanoparticles in the solid phase. The relative effectiveness in retaining gold nanoparticles in the solid phase for each functionalization strategy was determined to be, in descending order, in situ synthesis, template loading, and diffusion loading.     

Synthesis of Metallic Nanoparticles Using Closed‐Shell Structures as Templates

The synthesis and study of metallic nanoparticles are of continued and significant interest, with applications in materials science, catalysis, and medicine. The properties of metallic nanoparticles depend strongly on their particle size, shape, and interparticle distances. It is therefore desirable for the synthesis of metallic nanoparticles to be controlled for specific shapes and sizes. The rapid development in this research area has attracted intense interest from researchers with diverse expertise, and numerous methods towards the synthesis of monodisperse nanoparticles have been reported. In this Focus Review, we provide an overview of recent progress in the development of the template synthesis of metallic nanoparticles using closed‐shell structures, including biological molecules/assemblies and cage molecules.     

Synthesis of gold nanoparticles by microemulsion assisted photoreduction method

A new, clean, cost-effective and rapid method for the synthesis of stable spherical gold nanoparticles (AuNPs) is developed. This novel technique combines microemulsion as one of soft-nanotechnology techniques of wet chemistry, with photo-physics of UV-radiation in a unique versatile method to design and obtain controlled nanostructures for multifunctional materials. Based on a phase diagram in ternary water/Brij 30/n-heptane system pristine, and thiol functionalized, gold nanoparticles were obtained by a microemulsion assisted photoreduction technique, allowing increased flexibility during the synthesis and selection of materials. The spherical nanoparticles obtained by this route show a homogeneous size distribution, with an average diameter of 11 nm, for pristine gold nanoparticles and of 12 nm, for functionalized species. The evolution of the system at the nanoscale has been studied using, in tandem, UV-VIS and DLS measurements. The structure, size and shape of the final nanoparticles obtained have been evaluated by adequate instrumental techniques: FTIR, XRD and TEM image analysis. Kinetic studies have also been performed in order to follow the evolution of nanospecies during irradiation procedure.     

Microbial synthesis of gold nanoparticles: Current status and future prospects

Gold nanoparticles have been employed in biomedicine since the last decade because of their unique optical, electrical and photothermal properties. Present review discusses the microbial synthesis, properties and biomedical applications of gold nanoparticles. Different microbial synthesis strategies used so far for obtaining better yield and stability have been described. It also includes different methods used for the characterization and analysis of gold nanoparticles, viz. UV–visible spectroscopy, Fourier transform infrared spectroscopy, X ray diffraction spectroscopy, scanning electron microscopy, ransmission electron microscopy, atomic force microscopy, electron dispersive X ray, X ray photoelectron spectroscopy and cyclic voltametry. The different mechanisms involved in microbial synthesis of gold nanoparticles have been discussed. The information related to applications of microbially synthesized gold nanoparticles and patents on microbial synthesis of gold nanoparticles has been summarized.     

The in vitro and in vivo toxicity of gold nanoparticles

Gold nanoparticles,owing to their unique physicochemical and optical properties,well-established synthetic methods and easy modifications,have been widely used in biomedical science.Therefore,for their safe and efficient applications,much attention has been given to the toxicological evaluations of gold nanoparticles in biological systems.A large number of studies focusing on this problem have been carried out during the past years.However,the researches on gold nanoparticles toxicity still remain fragmentary and even contradictory with each other.This may be caused by the variety in experimental conditions.In this review,we aim to provide a better understanding about the in vitro and in vivo toxicity of gold nanoparticles by reviewing and describing the up to date literatures related to this problem and we mainly focused on these properties such as the particle size and shape,the surface charge and modification.Besides,we also summarized the adverse effect of gold nanoparticles on immune systems and analyzed the origin of the toxicity.     

Metal and Metal Oxide Nanostructures Prepared by Electrical Arc Discharge Method in Liquids

In this review, the importance of electrical arc discharge technique in liquids in synthesis of various nanostructures from carbon based materials to metal and metal oxide nanostructures with their general and specific properties, especially the photocatalytic performance of metal oxide nanostructures is studied. The effect of arc current on size distribution, morphology and physicochemical properties of metal and semiconductor nanostructures was investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS) and UV–Vis spectroscopy. WO₃ Cubic nanostructures with 30 nm mean particle size were formed during the discharge process in water. Discharge between zinc electrodes in water leads to formation of rod like and semi spherical ZnO nanostructures with 15–20 nm diameter range. ZrO₂ nanoparticles were formed using zirconium electrodes in water. Photodegradation of Rhodamine B (Rh. B) shows that the as prepared nanostructures in this method have potential ability for environmental purifications. Also, using silver electrodes in water leads to formation of silver nanoparticles with 8–15 nm average particle size. Moreover, a novel method for synthesis of gold nanoparticles without using gold electrodes is presented. Finally, the future outlook of this technique in synthesis of various nanocrystalline materials is presented.     

金纳米颗粒制备及应用研究进展

金纳米颗粒是近年研究的一种热门材料。介绍了金纳米颗粒主要的制备方法,包括化学还原法,两相法,晶种生长法以及模板法,并总结了金纳米粒子在生物医学、传感器、催化剂、电化学等领域的应用进展。     

Pillararene-based supramolecular systems for theranostics and bioapplications

As an emerging type of important macrocycles for supramolecular chemistry, pillararenes and their derivatives have been widely studied and applied in numerous fields, which intensively promotes the development of chemistry, materials science and biology.Pillararene-based theranostic systems are of special interest in the biological and medical areas as they have shown very promising results. Owing to easy preparation, reliable guest affinity, good biocompatibility and stability, pillararenes are frequently used to construct functional biomaterials. On one hand, pillararenes can either be used individually or form diversiform self-assemblies such as micelles, nanoparticles and vesicles to increase water solubility and biocompatibility of drugs.On the other hand, it is promising to modify solid materials like framework materials, silica nanoparticles and graphene oxides with pillararene derivatives to enhance their functions and controllability. In this review, we summarize recent endeavors of pillararene-based supramolecular systems with theranostics and other biological applications comprising drug delivery/chemotherapy, photodynamic/photothermal therapy, antimicrobials, bioimaging, etc. By introducing several typical examples, the design principles, preparation strategies, identifications and bio-applications of these pillararene-based supramolecular systems are described. Future challenges and directions of this field are also outlined.     

Synthesis,Characterization, and Applications of Copper Nanoparticles

Copper nanoparticles with different structural properties and effective biological effects may be fabricated using new green protocols. The control over particle size and in turn size-dependent properties of copper nanoparticles is expected to provide additional applications. Various methods for the synthesis of copper nanoparticles have been reported including chemical methods, physical methods, biological methods, and green synthesis. Biological methods involve the use of plant extracts, bacteria, and fungi. Commendable work has been done regarding the synthesis and stability of copper nanoparticles. There is a need to summarize the behavior of copper nanoparticles in different media under various conditions. Here, a complete list of the literature on the synthesis of copper nanoparticles, their properties, stabilizing agents, factors affecting the morphology, and their applications is presented. The importance of copper nanoparticles compared to other metal nanoparticles are due to high conductivity. Methods for the synthesis of copper nanoparticles, including green protocols using plants and micro-organisms compared chemical methods, have also been reviewed.     

Yolk-shell gold nanoparticles as model materials for support-effect studies in heterogeneous catalysis: Au, @C and Au, @ZrO2 for CO oxidation as an example

The use of nanostructured yolk-shell materials offers a way to discriminate support and particle-size effects for mechanistic studies in heterogeneous catalysis. Herein, gold yolk-shell materials have been synthesized and used as model catalysts for the investigation of support effects in CO oxidation. Carbon has been selected as catalytically inert support to study the intrinsic activity of the gold nanoparticles, and for comparison, zirconia has been used as oxidic support. Au, @C materials have been synthesized through nanocasting using two different nonporous-core@mesoporous-shell exotemplates: Au@SiO(2)@ZrO(2) and Au@SiO(2)@m-SiO(2). The catalytic activity of Au, @C with a gold core of about 14 nm has been evaluated and compared with Au, @ZrO(2) of the same gold core size. The strong positive effect of metal oxide as support material on the activity of gold has been proved. Additionally, size effects were investigated using carbon as support to determine only the contribution of the nanoparticle size on the catalytic activity of gold. Therefore, Au, @C with a gold core of about 7 nm was studied showing a less pronounced positive effect on the activity than the metal oxide support effect.     

Synthesis of a stable gold hydrosol by the reduction of chloroaurate ions by the amino acid, aspartic acid

Development of reliable protocols for the synthesis of nanoparticles of well-defined sizes and good monodispersity is an important aspect of nanotechnology. In this paper, we present details of the synthesis of gold nanoparticles of good monodispersity by the reduction of aqueous chloroaurate ions by the amino acid, aspartic acid. The colloidal gold solution thus formed is extremely stable in time, indicating electrostatic stabilization via nanoparticle surface-bound amino acid molecules. This observation has been used to modulate the size of the gold nanoparticles in solution by varying the molar ratio of chloroaurate ions to aspartic acid in the reaction medium. Characterization of the aspartic acid-reduced gold nanoparticles was carried out by UV-visible spectroscopy, thermogravimetric analysis and transmission electron microscopy. The use of amino acids in the synthesis and stabilization of gold nanoparticle in water has important implications in the development of new protocols for generation of bioconjugate materials.     

Rapid green synthesis of gold nanoparticles using Rosa hybrida petal extract at room temperature

This study reports a green method for the synthesis of gold nanoparticles using the aqueous extract of rose petals. The effects of gold salt concentration, extract concentration and extract quantity were investigated on nanoparticles synthesis. Gold nanoparticles were characterized with different techniques such as UV-vis spectroscopy, FT-IR spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, dynamic light scattering and transmission electron microscopy. Transmission electron microscopy experiments showed that these nanoparticles are formed with various shapes. FT-IR spectroscopy revealed that gold nanoparticles were functionalized with biomolecules that have primary amine group (-NH2), carbonyl group, -OH groups and other stabilizing functional groups. X-ray diffraction pattern showed high purity and face centered cubic structure of gold nanoparticles. Dynamic light scattering technique was used for particle size measurement, and it was found to be about 10nm. The rate of the reaction was high and it was completed within 5 min.     

Investigation of the core-shell interface in gold@silica nanoparticles: a silica imprinting approach

The nature of the self-assembled core-shell interface in gold@silica nanoparticles synthesized via a 3-aminopropyltrimethoxysilane (APTMS) route is investigated using materials synthesis as a sensitive tool for elucidating interfacial composition and organization. Our approach involves condensation of the gold@silica nanoparticles within a silica framework for synthesis of a composite gold-silica material containing approximately 30 wt % gold. This material contains one of the highest gold loadings reported, but maintains gold core isolation as ascertained via a single surface plasmon resonance absorption band frequency corresponding to that of gold nanoparticles in dilute aqueous solution. The immobilized gold cores are subsequently etched using cyanide anion for the synthesis of templated porosity, which corresponds to the space that was occupied by the gold. Characterization of immobilized amines is performed using probe molecule binding experiments, which demonstrate a lack of accessible amines after gold removal. Solid-state 13C CPMAS NMR spectroscopy on these materials demonstrates that the amount of amine immobilization must be less than 10% of the expected yield, assuming that all of the APTMS becomes bound to the gold nanoparticle template. These results require a core-shell interface in the gold@silica nanoparticles that is predominantly occupied by inorganic silicate species, such as Si-O-Si and Si-OH, rather than primary amines. Such a result is likely a consequence of the weak interaction between primary amines and gold in aqueous solution. Our method for investigating the core-shell interface of gold@silica nanoparticles is generalizable for other interfacial structures and enables the synthesis of bulk imprinted silica using colloidal templates.     

Analysis and applications of nanoparticles in the separation sciences: A case of gold nanoparticles

Nanometer-sized gold particles—gold nanoparticles (Au NPs)—are attracting a great deal of attention for their use in various technologies, including catalysis, optical and electronic devices, and separation science. In the emerging field of nanomaterials, the design, synthesis, and characterization of nanostructures are critical features because the manipulation of these structures has a direct effect on their resulting macroscopic properties. Nanostructures fabricated in layers on surfaces—for example, through self-assembly processes—have several potential applications in separation science. This review provides an introduction to the characterizations of Au NPs using size exclusion chromatography, high performance liquid chromatography (HPLC), and electrophoresis, and their self-assembly onto solid supports for analyses based on HPLC, gas chromatography, and capillary electrophoresis. In addition, sample concentration strategies involving the use of self-assembly approaches for surface modification of Au NPs are also discussed.     

Green synthesis of well-dispersed gold nanoparticles using Macrotyloma uniflorum

The synthesis of metal nanoparticles of different sizes, shapes, chemical composition and controlled monodispersity is an important area of research in nanotechnology because of their interesting physical properties and technological applications. Present work describes an eco-friendly method for the synthesis of spherical gold nanoparticles using aqueous extract of Macrotyloma uniflorum. The effects of quantity of extract, temperature and pH on the formation of nanoparticles are studied. The nanoparticles are characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and FTIR analysis. The high crystallinity of nanoparticles with fcc phase is evident from HRTEM images, SAED and XRD patterns. Synthesized nanoparticles have size in the range 14-17nm. FTIR spectrum indicates the presence of different functional groups present in the bio-molecule capping the nanoparticles. The possible mechanism leading to the formation of gold nanoparticles is suggested.     

Theranostic Approach for the Protein Corona of Polysaccharide Nanoparticles

Polysaccharide nanoparticles are promising materials in the wide range of disciplines such as medicine, nutrition, food production, agriculture, material science and others. They excel not only in their non‐toxicity and biodegradability but also in their easy preparation. As well as inorganic particles, a protein corona (PC) around polysaccharide nanoparticles is formed in biofluids. Moreover, it has been considered that the overall response of the organism to nanoparticles presence depends on the PC. This review summarises scientific publications about the structural chemistry of polysaccharide nanoparticles and their impact on theranostic applications. Three strategies of implementation of the PC in theranostics have been discussed: I) Utilisation of the PC in therapy; II) How the composition of the PC is analysed for specific disease markers; III) How the formed PC can interact with the immune system and enhances the immunomodulation or immunoelimination. Thus, the findings from this review can contribute to improve the design of drug delivery systems. However, it is still necessary to elucidate the mechanisms of nano‐bio interactions and discover new connections in nanoscale research.     

Sol–gel synthesis of porous inorganic materials using “core–shell” latex particles as templates

Here we report on the sol–gel synthesis of porous inorganic materials based on manganese, molybdenum, and tungsten compounds using the “core–shell” siloxane-acrylate latex as a template. The chemical composition and structural characteristics of the materials obtained have been investigated. It was shown that temperature conditions and gaseous media composition during the template destruction controlled the composition and structure of porous materials. To obtain porous inorganic materials for catalytic applications, the “core–shell” latex template was preliminarily functionalized by gold and palladium nanoparticles obtained by thermal reduction of noble metal ions-precursors in a polycarboxylic “shell”. Upon the template removal, noble metals nanoparticles of a size of dozens of nanometers were homogeneously distributed in the material porous structure. The evaluation of the catalytic activity of macroporous manganese, tungsten, and molybdenum oxides under the conditions of liquid phase catalytic oxidation of organic dyes has been performed. The prospects of employing macroporous oxide systems with immobilized nanoparticles of noble metals in the processes of hydrothermal oxidation of radionuclide organic complexes in radioactive waste decontamination have been demonstrated.     

Facile synthesis and functionalization of water-soluble gold nanoparticles for a bioprobe

In this work, we report the size tunable synthesis of water-dispersed gold nanoparticles by using octadecylamine (ODA) as the reducing agent, that electrostatically complexes with the chloroaurate ions, reduces them, and subsequently caps the gold nanoparticles. Amine-capped gold nanoparticles, thus formed, were subsequently coordinated with a secondary monolayer of an anionic surfactant, sodium bis(2-ethylhexyl)-sulfosuccinate (AOT) which helps in providing sufficient hydrophilicity to the gold nanoparticles. Functionalized gold nanoparticles were characterized by UV-vis, IR spectrophotometric, dynamic light scattering, zeta-potential and transmission electron microscopic techniques, which demonstrated high stability of gold nanoparticles in aqueous media, indicating stabilization via bilayers of ODA and AOT. The gold nanoparticles were further conjugated with a protein (bovine serum albumin) and the interaction was investigated by circular dichroism studies as well as by measuring the fluorescence quenching of the tryptophan residues of protein molecules after the binding of nanoparticles to specific sites of the protein. The binding constant and the stoichiometry values indicated that the particles with larger core size are less site-specific but show higher binding affinity with protein molecules. The use of a bio-compatible synthetic process and the stabilization of the gold nanoparticles by ODA and AOT are interesting from the point of view of making bioprobes for life science applications.     

A gold nanoparticle-based immunochromatographic assay: the influence of nanoparticulate size

Four different sized gold nanoparticles (14 nm, 16 nm, 35 nm and 38 nm) were prepared to conjugate an antibody for a gold nanoparticle-based immunochromatographic assay which has many applications in both basic research and clinical diagnosis. This study focuses on the conjugation efficiency of the antibody with different sized gold nanoparticles. The effect of factors such as pH value and concentration of antibody has been quantificationally discussed using spectra methods after adding 1 wt% NaCl which induced gold nanoparticle aggregation. It was found that different sized gold nanoparticles had different conjugation efficiencies under different pH values and concentrations of antibody. Among the four sized gold nanoparticles, the 16 nm gold nanoparticles have the minimum requirement for antibody concentrations to avoid aggregation comparing to other sized gold nanoparticles but are less sensitive for detecting the real sample compared to the 38 nm gold nanoparticles. Consequently, different sized gold nanoparticles should be labeled with antibody under optimal pH value and optimal concentrations of antibody. It will be helpful for the application of antibody-labeled gold nanoparticles in the fields of clinic diagnosis, environmental analysis and so on in future.