In Vitro and In Vivo Evaluation of PEGylated Layer‐by‐Layer Polyelectrolyte‐Coated Paclitaxel Nanocrystals

Drug nanocrystals (NCs) are colloidal dispersions composed almost entirely of drug. As such, there is substantial interest in targeting them to diseased tissues, where they can locally deliver high doses of the therapeutic. However, because of their uncontrolled dissolution characteristics in vivo and uptake by the monomolecular phagocyte system, achieving tumor accumulation is challenging. To address these issues, a layer‐by‐layer approach is adopted to coat paclitaxel NCs with alternating layers of oppositely charged polyelectrolytes, using a PEGylated copolymer as the top layer. The coating successfully slows down dissolution in comparison to the noncoated NCs and to Abraxane (an approved paclitaxel nanoformulation), provides colloidal stability in physiologically relevant media, and has no intrinsic effect on cell viability at the concentrations tested. Nevertheless, their pharmacokinetic and biodistribution profile indicates that the NCs are rapidly cleared from the bloodstream followed by accumulation in the mononuclear phagocyte system organs (i.e., liver and spleen). This is hypothesized to be a consequence of the shedding of the PEGylated polyelectrolyte from the NCs' surface. While therapeutic efficacy was not investigated (due to poor tumor accumulation), overall, this work questions whether approaches that rely solely on electrostatic interactions for retaining coatings on the surfaces of NCs are appropriate for use in vivo.     

Cytotoxicity of BSA‐Stabilized Gold Nanoclusters: In Vitro and In Vivo Study

Gold nanoclusters (Au NCs) are one of the most promising fluorescent nanomaterials for bioimaging, targeting, and cancer therapy due to their tunable optical properties, yet their biocompatibility still remains unclear. Herein, the cytotoxicity of bovine serum albumin (BSA)‐stabilized Au NCs is studied by using three tumor cell lines and two normal cell lines. The results indicate that Au NCs induce the decline of cell viabilities of different cell lines to varying degrees in a dose‐ and time‐dependent manner, and umbilical vein endothelial cells which had a higher intake of Au NCs than melanoma cells show more toxicity. Addition of free BSA to BSA‐Au NCs solutions can relieve the cytotoxicity, implying that BSA can prevent cell damage. Moreover, Au NCs increase intracellular reactive oxygen species (ROS) production, further causing cell apoptosis. Furthermore, N‐acetylcysteine, a ROS scavenger, partially reverses Au NCs‐induced cell apoptosis and cytotoxicity, indicating that ROS might be one of the primary reasons for the toxicity of BSA‐Au NCs. Surprisingly, Au NCs with concentrations of 5 and 20 nM significantly inhibit tumor growth in the xenograft mice model of human liver cancer, which might provide a new avenue for the design of anti‐cancer drug delivery vehicles.     

Enhanced Fluorescence of Gold Nanoclusters Composed of HAuCl4 and Histidine by Glutathione: Glutathione Detection and Selective Cancer Cell Imaging

Glutathione (GSH) can significantly and selectively enhance the fluorescence intensity of Au nanoclusters (NCs) prepared by blending HAuCl₄ and histidine in solution. The quantum yield of the Au NCs after adding GSH can reach above 10%. Besides, GSH capping shifts the excitation peak of Au NCs from ultraviolet (386 nm) to visible light (414 nm) and improves the stability of the Au NCs. The cytotoxicities of the Au NCs with and without GSH for normal lung cells (ATII) and cancerous lung cells (A549) are evaluated. The GSH‐capped Au NCs have much less cytotoxicity to both normal and cancer cells, as compared to those without GSH. For Au NCs without GSH, less cytotoxicity is observed in cancer cells than in normal cells. In addtion, the Au NCs can selectively detect GSH over cysteine and homocysteine, the two biothiols which commonly exist in cells that can seriously affect GSH detection. Most importantly, Au NCs without GSH can selectively image the cancer cells, especially for the liver cancer cells whose GSH content is much higher than other cell types. This property makes the Au NCs a powerful probe to distinguish cancer cells from normal cells.     

Verification of unzipping models of electromigration in gold nanocontacts by in situ high-resolution transmission electron microscopy

We observed in situ the electromigration process of gold (Au) nanocontacts (NCs) by high-resolution transmission electron microscopy. The structural dynamics of the interior and surfaces of the NCs were investigated at the atomic level. In particular, we directly verified the evidence of the unzipping model of electromigration with the in situ observation of surface-edge movement. The fundamental parameters of NCs, i.e., conductance and tensile force, were also measured during in situ lattice imaging of electromigration. Atoms migrating from the negative electrode accumulated at the most constricted regions of the NCs, leading to expansion. As a result, the NCs were compressed by the two electrodes. We demonstrated the magnitude of the force acting on the NCs during electromigration. The critical voltage of electromigration was approximately 80 mV, and the current density at the critical voltage was 60 TA m(-2). We found that Au nanogaps could be fabricated by applying this bias voltage to Au NCs.     

Controlled Integration of Nanocrystals in Inverted Hexagonal Nano‐Pits at the Surface of Light‐Emitting Heterostructures (Adv. Mater. 5/2008)

Hexagonal inverted nanopyramids on gallium‐nitride‐based multiple quantum wells are exploited to confine gold nanocrystals (NCs) at the surface of such light‐emitting heterostructures. The number of NCs incorporated in each pit can be controlled by nanoengineering either the NCs' size or the pit size. Capillarity effects can be used to drive the formation of well‐defined assemblies of Au NCs within each pit, as reported by Sérgio Pereira and co‐workers on p. 1038.     

2D Binary Plasmonic Nanoassemblies with Semiconductor n/p‐Doping‐Like Properties

The electronic, optical, thermal, and magnetic properties of an extrinsic bulk semiconductor can be finely tuned by adjusting its dopant concentration. Here, it is demonstrated that such a doping concept can be extended to plasmonic nanomaterials. Using two‐dimensional (2D) assemblies of Au@Ag and Au nanocubes (NCs) as a model system, detailed experimental and theoretical studies are carried out, which reveal collective semiconductor n/p‐doping‐like plasmonic properties. A threshold doping concentration of Au@Ag NCs is observed, below which p‐doping dominates and above which n‐doping prevails. Furthermore, Au@Ag NC dopants can be converted into corresponding Au seed “voids” dopants by selectively removing Ag without changing the overall structural integrity. The results show that the plasmonic doping concept may serve as a general design principle guiding synthesis and assembly of plasmonic metamaterials for programmable optoelectronic devices.     

Colloid‐Interface‐Assisted Laser Irradiation of Nanocrystals Superlattices to be Scalable Plasmonic Superstructures with Novel Activities

High‐efficient charge and energy transfer between nanocrystals (NCs) in a bottom‐up assembly are hard to achieve, resulting in an obstacle in application. Instead of the ligands exchange strategies, the advantage of a continuous laser is taken with optimal wavelength and power to irradiate the film‐scale NCs superlattices at solid–liquid interfaces. Owing to the Au‐based NCs' surface plasmon resonance (SPR) effect, the gentle laser irradiation leads the Au NCs or Au@CdS core/shell NCs to attach each other with controlled pattern at the interfaces between solid NCs phase and liquid ethanol/ethylene glycol. A continuous wave 532 nm laser (6.68–13.37 W cm^?2), to control Au‐based superlattices, is used to form the monolayer with uniformly reduced interparticle distance followed by welded superstructures. Considering the size effect to Au NCs' melting, when decreasing the Au NCs size to ≈5 nm, stronger welding nanostructures are obtained with diverse unprecedented shapes which cannot be achieved by normal colloidal synthesis. With the help of facile scale‐up and formation at solid–liquid interfaces, and a good connection of crystalline between NCs, the obtained plasmonic superstructured films that could be facilely transferred onto different substrates exhibit broad SPR absorption in the visible and near‐infrared regime, enhanced electric conductivities, and wide applications as surface enhanced Raman scattering (SERS)‐active substrates.     

Au‐Edged CuZnSe2 Heterostructured Nanosheets with Enhanced Electrochemical Performance

Two‐dimensional (2D) nanomaterials and heterostructured nanocrystals (NCs) are two hot topics in current nanoresearch. However, reports on heterostructured NCs with 2D features are still rare. In this work, we demonstrate a one‐pot colloidal chemistry route for synthesizing Au‐CuZnSe₂ heterostructures with spherical Au domains attached to the edge of a sheet of CuZnSe₂. This protocol involves the preferential formation of Au clusters and the seeded growth of CuZnSe₂ sheets because of the lattice matching of CuSe with Au. As an example to demonstrate the importance of such heterostructures, the electrochemical performance of Au‐CuZnSe₂ heterostructured nanosheets is compared with that of heterostructured nanorods, Au NCs, and CuZnSe₂ NCs. The heterostructured nanosheets exhibit the best electrochemical activity.     

Molecule‐Induced p‐Doping in Perovskite Nanocrystals Enables Efficient Color‐Saturated Red Light‐Emitting Diodes

Color‐saturated red light‐emitting diodes (LEDs) with emission wavelengths at around 620–640 nm are an essential part of high‐definition displays. Metal halide perovskites with very narrow emission linewidth are promising emitters, and rapid progress has been made in perovskite‐based LEDs (PeLEDs); however, the efficiency of the current color—pure red PeLEDs—still far lags behind those of other‐colored ones. Here, a simple but efficient strategy is reported to gradually down‐shift the Fermi level of perovskite nanocrystals (NCs) by controlling the interaction between NCs and their surface molecular electron acceptor—benzyl iodide with aromatic rings—and realize p‐doping in the color‐saturated 625 nm emitting NCs, which significantly reduces the hole injection barrier in devices. Besides, both the luminescence efficiency and electric conductivity of perovskite NCs are enhanced as additional advantages as the result of surface defects passivation. As a result, the external quantum efficiency for the resulting LED is increased from 4.5% to 12.9% after benzyl iodide treatment, making this device the best‐performing color‐saturated red PeLED so far. It is further found that the hole injection plays a more critical role than the photoluminescence efficiency of perovskite emitter in determining the LED performance, which implies design principles for efficient thin‐film planar LEDs.     

Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution

The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs. In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen. The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent.     

In vivo Quantum‐Dot Toxicity Assessment

Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe–ZnS core–shell quantum dots in healthy Sprague–Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5–15.0 nmol) over short‐term (<7 days) and long‐term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.     

Electrogenerated chemiluminescence of Au nanoclusters for the detection of dopamine

Electrogenerated chemiluminescence (ECL) emission was observed from the water-soluble, bovine serum albumin (BSA)-stabilized Au nanoclusters for the first time. The possible ECL mechanism was discussed according to the presented results and ascribed to the effective electron transfer from the conduction-band of excited indium tin oxide (ITO) to Au nanoclusters (NCs). A simple label-free method for the detection of dopamine has been developed based on the Au NCs ECL in aqueous media. The Au NCs could be an effective candidate for new types of ECL biosensors in the future due to their fascinating features, such as good water solubility, low toxicity, ease of labeling, and excellent stability.     

Surfactant‐Concentration‐Dependent Shape Evolution of Au–Pd Alloy Nanocrystals from Rhombic Dodecahedron to Trisoctahedron and Hexoctahedron

The surface structure‐controlled synthesis of noble metal nanocrystals (NCs) bounded by high‐index facets has become a hot research topic due to their potential to significantly improve catalytic performance. This study reports the preparation of monodisperse Au–Pd alloy NCs with systematic shape evolution from rhombic dodecahedral (RD) to trisoctahedral (TOH), and hexoctahedral (HOH) structures by varying the concentration of surfactant in the surfactant‐mediated synthesis. The as‐prepared three kinds of alloy NCs possess almost the same size and composition as each other. It is suggested that the surfactant containing long‐chain octadecyltrimethyl ammonium (OTA⁺) ions plays a key role in the formation of high index facets, and the crystal growth kinetics may also have an effect on the formation of different nanocrystal morphologies. In addition, the catalytic activities of these NCs are evaluated by structure‐sensitive reactions, including ethanol electro‐oxidation and the catalytic reduction of 4‐nitrophenol (4‐NPh). These three types of Au–Pd alloy NCs exhibit different catalytic selectivities towards these two reactions. The catalytic activities toward electro‐oxidation of ethanol are in the order of HOH > RD > TOH, which follows the order of their corresponding surface energies. However, the activities toward catalytic reduction of 4‐NPh are in the order of RD > TOH > HOH, which should be related to the local structure of the surfaces.     

Self‐Assembled Au/CdSe Nanocrystal Clusters for Plasmon‐Mediated Photocatalytic Hydrogen Evolution

Plasmon‐mediated photocatalytic systems generally suffer from poor efficiency due to weak absorption overlap and thus limited energy transfer between the plasmonic metal and the semiconductor. Herein, a near‐ideal plasmon‐mediated photocatalyst system is developed. Au/CdSe nanocrystal clusters (NCs) are successfully fabricated through a facile emulsion‐based self‐assembly approach, containing Au nanoparticles (NPs) of size 2.8, 4.6, 7.2, or 9.0 nm and CdSe quantum dots (QDs) of size ≈3.3 nm. Under visible‐light irradiation, the Au/CdSe NCs with 7.2 nm Au NPs afford very stable operation and a remarkable H₂‐evolution rate of (10× higher than bare CdSe NCs). Plasmon resonance energy transfer from the Au NPs to the CdSe QDs, which enhances charge‐carrier generation in the semiconductor and suppresses bulk recombination, is responsible for the outstanding photocatalytic performance. The approach used here to fabricate the Au/CdSe NCs is suitable for the construction of other plasmon‐mediated photocatalysts.     

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface‐engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.     

Chirality and Surface Bonding Correlation in Atomically Precise Metal Nanoclusters

Chirality is ubiquitous in nature and occurs at all length scales. The development of applications for chiral nanostructures is rising rapidly. With the recent achievements of atomically precise nanochemistry, total structures of ligand-protected Au and other metal nanoclusters (NCs) are successfully obtained, and the origins of chirality are discovered to be associated with different parts of the cluster, including the surface ligands (e.g., swirl patterns), the organic–inorganic interface (e.g., helical stripes), and the kernel. Herein, a unified picture of metal–ligand surface bonding-induced chirality for the nanoclusters is proposed. The different bonding modes of M–X (where M = metal and X = the binding atom of ligand) lead to different surface structures on nanoclusters, which in turn give rise to various characteristic features of chirality. A comparison of Au–thiolate NCs with Au–phosphine ones further reveals the important roles of surface bonding. Compared to the Au–thiolate NCs, the Ag/Cu/Cd–thiolate systems exhibit different coordination modes between the metal and the thiolate. Other than thiolate and phosphine ligands, alkynyls are also briefly discussed. Several methods of obtaining chiroptically active nanoclusters are introduced, such as enantioseparation by high-performance liquid chromatography and enantioselective synthesis. Future perspectives on chiral NCs are also proposed.     

新型神经调控用TiO2-Au光电转换纳米复合物性能研究

本文提出了一种基于光电转换纳米复合物(NCs)的新型神经调控方式。NCs是TiO₂纳米晶表面连接金纳米粒子的复合物, 可产生光电流并有效引发神经细胞去极化。在405 nm光照射下, NCs产生的光电流比单一TiO₂纳米晶产生的光电流强度显著提高。PC12细胞上的膜电位荧光探针和钙离子荧光探针测试结果显示, 在405 nm光照下, 经NCs处理的细胞发生去极化。在活体抗癫痫实验中进一步证明, NCs产生的光电流可明显减轻斑马鱼的癫痫发作。本研究结果表明NCs可进行神经调控, 对神经疾病的治疗具有重要意义。     

Enhanced Photocarrier Generation with Selectable Wavelengths by M‐Decorated‐CuInS2 Nanocrystals (M = Au and Pt) Synthesized in a Single Surfactant Process on MoS2 Bilayers

A facile approach for the synthesis of Au‐ and Pt‐decorated CuInS₂ nanocrystals (CIS NCs) as sensitizer materials on the top of MoS₂ bilayers is demonstrated. A single surfactant (oleylamine) is used to prepare such heterostructured noble metal decorated CIS NCs from the pristine CIS. Such a feasible way to synthesize heterostructured noble metal decorated CIS NCs from the single surfactant can stimulate the development of the functionalized heterostructured NCs in large scale for practical applications such as solar cells and photodetectors. Photodetectors based on MoS₂ bilayers with the synthesized nanocrystals display enhanced photocurrent, almost 20–40 times higher responsivity and the On/Off ratio is enlarged one order of magnitude compared with the pristine MoS₂ bilayers‐based photodetectors. Remarkably, by using Pt‐ or Au‐decorated CIS NCs, the photocurrent enhancement of MoS₂ photodetectors can be tuned between blue (405 nm) to green (532 nm). The strategy described here acts as a perspective to significantly improve the performance of MoS₂‐based photodetectors with the controllable absorption wavelengths in the visible light range, showing the feasibility of the possible color detection.     

High‐Pressure‐Induced Comminution and Recrystallization of CH3NH3PbBr3 Nanocrystals as Large Thin Nanoplates

High pressure (HP) can drive the direct sintering of nanoparticle assemblies for Ag/Au, CdSe/PbS nanocrystals (NCs). Instead of direct sintering for the conventional nanocrystals, this study experimentally observes for the first time high‐pressure‐induced comminution and recrystallization of organic–inorganic hybrid perovskite nanocrystals into highly luminescent nanoplates with a shorter carrier lifetime. Such novel pressure response is attributed to the unique structural nature of hybrid perovskites under high pressure: during the drastic cubic–orthorhombic structural transformation at ≈2 GPa, (301) the crystal plane fully occupied by organic molecules possesses a higher surface energy, triggering the comminution of nanocrystals into nanoslices along such crystal plane. Beyond bulk perovskites, in which pressure‐induced modifications on crystal structures and functional properties will disappear after pressure release, the pressure‐formed variants, i.e., large (≈100 nm) and thin (<10 nm) perovskite nanoplates, are retained and these exhibit simultaneous photoluminescence emission enhancing (a 15‐fold enhancement in the photoluminescence) and carrier lifetime shortening (from ≈18.3 ± 0.8 to ≈7.6 ± 0.5 ns) after releasing of pressure from 11 GPa. This pressure‐induced comminution of hybrid perovskite NCs and a subsequent amorphization–recrystallization treatment offer the possibilities of engineering the advanced hybrid perovskites with specific properties.     

Preclinical evaluation of Raman nanoparticle biodistribution for their potential use in clinical endoscopy imaging

Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.