Supramolecules‐Guided Synthesis of Brightly Near‐Infrared Au22 Nanoclusters with Aggregation‐Induced Emission for Bioimaging

Protein‐protected gold nanoclusters with emission in the near‐infrared wavelength range have been widely considered for applications in biomedical fields. However, their quantum yield (QY) remains low, thus limiting their practical applications. Herein, a novel strategy to synthesize bovine serum albumin–encapsulated gold nanoclusters (BSA‐AuNCs) with QY of 23% is developed. Assembled coordination polymers (supramolecules) of Au(I)‐BSA complexes are initially formed because of the intermolecular forces between BSA ligands. The forces are easily controlled by pH level during the reaction, leading to significant change in the photoluminescence of BSA‐AuNCs. By regulating the pH and reaction temperature, Au(0)@Au(I) core‐shell structured BSA‐AuNCs are fabricated in 2 h. Importantly, such AuNCs are in a rigidified state with high Au(I) content in the shell, offering an explanation for their high luminescence character. Further increasing QY to 29% is achieved by confining BSA‐AuNCs into a cationic polymer, poly(allylamine) hydrochloride (AuNCs@PAH). Enhanced cellular uptake and improved sensitivity of AuNCs@PAH to glutathione compared to BSA‐AuNCs is demonstrated. These findings may give insights into the synergistic effect of pH level and reaction temperature on the properties of protein‐encapsulated AuNCs and provide a possible way for up‐scaled fabrication of brighter AuNCs protected by other protein templates.     

Red Emissive Biocompatible Nanoparticles from Tetraphenylethene‐Decorated BODIPY Luminogens for Two‐Photon Excited Fluorescence Cellular Imaging and Mouse Brain Blood Vascular Visualization

BODIPY (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene) is an emissive chromophore in solutions but suffers from fluorescence quenching when aggregated due to its flat molecular conformation and small Stokes shift. To create aggregate‐state emissive BODIPY luminogens, tetraphenylethene (TPE), which is a popular luminogen with intriguing aggregation‐induced emission (AIE) characteristic, is introduced as periphery to a methylated BODIPY core. Three TPE‐BODIPY adducts are synthesized and characterized, and their photophysical properties and electronic structures are investigated. The incorporation of AIE‐active TPE units alleviates aggregation‐caused quenching of BODIPY core, furnishing emissive nanoparticles based on TPE‐BODIPY adducts. Significantly, the two‐photon absorption (TPA) and two‐photon excited fluorescence (TPEF) properties are improved as more TPE units are attached. The luminogens with 3TPE units (3TPE‐BODIPY) shows the strongest TPA and TPEF in the wavelength range of 750–830 nm, with cross‐section values of 264 and 116 GM at 810 nm, respectively. Red emissive nanoparticles with a Stokes shift of 60 nm and a fluorescence quantum yield of 16% are attained by encapsulating 3TPE‐BODIPY with 1,2‐sistearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000]. The nanoparticles are biocompatible and function well in TPEF cellular imaging and mouse brain blood vascular visualization.     

Copper Sulfide Nanodisks and Nanoprisms for Photoacoustic Ovarian Tumor Imaging

Transvaginal ultrasound is widely used for ovarian cancer screening but has a high false‐positive rate. Photoacoustic imaging provides additional optical contrast to supplement ultrasound and might be able to improve the accuracy of screening. Two copper sulfide (CuS) nanoparticle types (nanodisks and triangular nanoprisms) are reported as photoacoustic contrast agents for imaging ovarian cancer. Both CuS nanoprisms and nanodisks are ≈6 nm thick and ≈26 nm wide and are coated with poly(ethylene glycol) to make them colloidally stable in phosphate‐buffered saline for at least two weeks. The CuS nanodisks and nanoprisms reveal strong localized surface plasmon resonances with peak maxima at 1145 and 1098 nm, respectively. Both nanoparticle types have strong and stable photoacoustic intensity with detection limits below 120 pm . The circular CuS nanodisk remains in the circulation of nude mice (n = 4) and xenograft 2008 ovarian tumors (n = 4) 17.9‐fold and 1.8‐fold more than the triangular nanoprisms, respectively. Finally, the photoacoustic intensity of the tumors from the mice (n = 3) treated with CuS nanodisks is threefold higher than the baseline. The tumors treated with nanodisks have a characteristic peak at 920 nm in their spectrum to potentially differentiate the tumor from adjacent tissues.     

Green Template‐Free Synthesis of Mesoporous Ternary CoNi–Mn Oxide Nanowires Towards High‐Performance Electrochemical Capacitors

One‐dimensional (1D) mesoporous ternary Co–Ni–Mn oxide nanowires (CNMO NWs) have been controllably fabricated via a facile yet scalable template‐free strategy involving a green hydrothermal route coupled with the following calcination. The composition of the reaction solvent system, i.e., the volume ratio of the ethylene glycol and deionized water, plays a significant role in tuning the specific morphologies and microstructures of the final CNMO products. The as‐derived lD CNMO NWs are constructed with numerous nanoparticle subunits with the size of ≈5–10 nm, and possess lots of interparticle mesopores ranged from 2 to 6 nm. The well‐defined mesoporous CNMO NWs apparently have appealing structural advantages, such as fast and convenient electron and ion transport, sufficient redox electrochemical centers with multiple valences, and large electroactive surface area. As a result, the as‐fabricated mesoporous CNMO NWs manifest exceptional pesudocapacitance and excellent cycling stability at high rates when evaluated as a striking low‐cost electrode for next‐generation electrochemical capacitors.     

Upconverting nanoparticles for pre‐clinical diffuse optical imaging,microscopy and sensing: Current trends and future challenges

Upconverting nanoparticles (UCNPs) are a class of recently developed luminescent biomarkers that – in several aspects – are superior to organic dyes and quantum dots. UCNPs can emit spectrally narrow anti‐Stokes shifted light with quantum yields which greatly exceed those of two‐photon dyes for fluence rates relevant for deep tissue imaging. Compared with conventionally used Stokes‐shifting fluorophores, UCNP‐based imaging systems can acquire completely autofluorescence‐free data with superb contrast. For diffuse optical imaging, the multi‐photon process involved in the upconversion process can be used to obtain images with unprecedented resolution. These unique properties make UCNPs extremely attractive in the field of biophotonics. UCNPs have already been applied in microscopy, small‐animal imaging, multi‐modal imaging, highly sensitive bioassays, temperature sensing and photodynamic therapy. In this review, the current state‐of‐the‐art UCNPs and their applications for diffuse imaging, microscopy and sensing targeted towards solving essential biological issues are discussed.     

Surface modification of magnetite nanoparticles for biomedical applications

The preparation of magnetite nanoparticles with narrow size distributions using poly(ethylene glycol) (PEG-COOH) or carboxymethyl dextran (CMDx) chains covalently attached to the particle surface using carbodiimide chemistry is described. Particles were synthesized by thermal decomposition and modified with 3-aminopropyl trimethoxysilane (APS) to render particles with reactive amine groups (-NH₂) on their surface. Amines were then reacted with carboxyl groups in PEG-COOH or CMDx using carbodiimide chemistry in water. The size and stability of the functionalized magnetic nanoparticles was studied as a function of pH and ionic strength using dynamic light scattering and zeta potential measurements.     

Probing Chemical and Mechanical Nanodomains in Copolymer Nanorods with Correlative Atomic Force Microscopy—Nano‐correscopy

The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limited resolution, are unable to map these properties correlatively at nanoscale. An innovative use of atomic force microscopy‐based techniques, namely nano‐correscopy, overcomes this limitation and offers multiprobe capability to map mechanical (viscous and elastic) and chemical domains of nanoparticles correlatively. The strengths of this approach are demonstrated using polymer composite nanorods: m‐PEG‐PLGA ((m‐PEG–methoxy‐poly (ethylene glycol)‐b‐poly (lactic‐co‐glycolic) acid). Precise distribution of PLGA (monomers of lactide and glycolide) and poly(ethylene glycol) (PEG) polymer across nanorods is identified. The hydrophobic lactide component is found predominantly at the apex, while hydrophilic glycolide and PEG assembled at the body of the nanorods and correlate with a gradient of nanomechanical properties. New knowledge of how both nanochemical domains and nanomechanical properties are distributed across the nanorod will allow elucidating the interactions of nanorods with the proteins and biomolecules in the future, which will directly influence the fate of nanorods in vivo and will guide new synthesis methods.     

Structure and composition of nanotubes formed during the anode oxidation of titanium

The structure and composition of nanotubes ≈1.5 μm long and ≈100 nm in diameter, formed electrolytically on the surfaces of titanium plates in a two-electrode cell at room temperature in a 0.5 wt % NH4F solution in ethylene glycol and glycerin, were studied by analytical and diffraction transmission electron microscopy.     

Cross‐Linked Proteins with Gold Nanoclusters: A Dual‐Purpose pH‐Responsive Material for Controllable Cell Imaging and Antibiotic Delivery

This report describes the development of a facile method for the synthesis of cross‐linked proteins with gold nanoclusters (CP‐GNC). The synthesis reaction is completed within 15 min at 97 °C. The synthesized CP‐GNC are characterized by using UV–vis absorption, fluorescence, X‐ray photoelectron spectroscopy, and transmission electron microscopy. CP‐GNC are approximately 100 nm in diameter and 700 nm in length, whereas AuNCs within the nanorods are approximately 6 nm in size. These materials are highly fluorescent with quantum yield of 7.2% and can be absorbed onto and release from bacterial cells in a pH‐dependent and reversible manner. The recent data show that CP‐GNC can be a useful, new tool with potential applications in fluorescent cell imaging and antibiotic targeting.     

Facile One‐Pot Conversion of Petroleum Asphaltene to High Quality Green Fluorescent Graphene Quantum Dots and Their Application in Cell Imaging

Benefiting from the natural nano‐size graphene‐structure in natural asphaltene material, a facile one‐pot route, mild chemical oxidation of low‐value petroleum asphaltene followed by routine ammonium neutralization, is presented to produce high quality graphene quantum dots (GQDs). The asphaltene‐derived GQDs possess a variety of oxygen‐containing and nitrogen‐containing functional groups such as carboxyl, hydroxyl, amine, and nitro groups. They present such excellent fluorescence properties as stable ability to retain strong green fluorescence within a relative broad excitation range in a bio‐suitable pH range of 4–7, high photoluminescence quantum yield of 18% and good fluorescent stability against photobleaching. And they are much smaller and thinner than most reported GQDs, displaying good biocompatibility with low cytotoxicity, effective cellular uptake, and excellent fluorescent probe performance for cancer cell imaging.     

Development of a Liver‐Targeting Gold–PEG–Galactose Nanoparticle Platform and a Structure–Function Study

For the specific liver parenchymal cell delivery, a series of short heterobifunctional poly(ethylene glycol) (PEG) derivatives containing dimercapto and galactose (Gal) terminals is synthesized for the preparation of gold conjugates. The Gal density on the surface of all gold conjugates can be well controlled and the prepared gold conjugates are stable in various media, even in the presence of serum. For the liver targeting and reflectance imaging applications, the structure–function relationships of this platform, including the influence of the PEG molecular weight and the Gal ligand coverage of hybrid particles on the cytotoxicity and cellular recognition of tumor cells in vitro and on their liver‐targeting ability in small animals, are studied. Biocompatibility results show that HepG2 cells are more sensitive than HeLa cells to gold conjugates. Cellular uptake studies demonstrate that a lower PEG molecular weight, a higher Gal density, or a higher gold concentration can increase the cellular uptake efficiency of these hybrid particles in HepG2 cells when the other parameters are constant. The results reveal the importance of parameter modulation for the design and control of nanoprobes and the gold conjugates with short PEG chains and a high Gal density are a potential vector for active‐targeting therapy.     

Fullerene‐Structural Carbon‐Based Dots from C60 Molecules and their Optical Properties

Fullerene‐structural carbon‐based dots (f‐CDs) are synthesized for the first time by chemically oxidizing fullerene molecules (C₆₀) using concentrated HNO₃. The lateral sizes of the f‐CDs distribute in the range of 7–20 nm, and the heights mainly range from 0.4 to 1.3 nm with an average value of 0.7 nm. The presence of massive pentagonal carbon units makes the f‐CDs different from most of graphitic‐CDs in structure and morphology. The f‐CDs exhibit unique luminescent properties such as photoluminescence (PL) and electrochemiluminescence. Based on the investigation of the UV–vis absorption and luminescent properties, a novel and reasonable model is proposed for the PL mechanism of f‐CDs. Furthermore, the obtained f‐CDs show low cytotoxicity and have potential application in cell imaging.     

Hydrothermal Preparation of Photoluminescent Graphene Quantum Dots Characterized Excitation‐Independent Emission and its Application as a Bioimaging Reagent

Zero‐dimensional photoluminescent (PL) graphene quantum dots (GQDs) that can be used as the cell‐imaging reagent are prepared by a hydrothermal route using the graphene oxide (GO) as the carbon source. Under the optimized hydrothermal conditions, an initial hydrogen peroxide concentration of 0.5 mg mL^?1 at 180 °C for 120 min, the GO sheets can be cut into nanocrystals with lateral dimensions in the range of 1.5–5.5 nm and an average thickness of around 1.1 nm. The as‐prepared GQDs exhibit an abundance of hydrophilic hydroxy and carboxyl groups and emit bright blue luminescence with up‐conversion properties in a water solution at neutral pH. Most interestingly, they indicate excitation‐independent emission characteristics, and the surface state is demonstrated to have a key role in the PL properties. The fluorescence quantum yield of the GQDs is tested to be around 6.99% using quinine sulfate as a standard. In addition, the as‐prepared GQDs can enter into HeLa cells easily as a fluorescent imaging reagent without any further functionalization, indicating they are aqueous stability, biocompatibility, and promising for potential applications in biolabeling and solution state optoelectronics.     

Systemic Administration of Polymer‐Coated Nano‐Graphene to Deliver Drugs to Glioblastoma

Graphene—2D carbon—has received significant attention thanks to its electronic, thermal, and mechanical properties. Recently, nano‐graphene (nGr) has been investigated as a possible platform for biomedical applications. Here, a polymer‐coated nGr to deliver drugs to glioblastoma after systemic administration is reported. A biodegradable, biocompatible poly(lactide) (PLA) coating enables encapsulation and controlled release of the hydrophobic anticancer drug paclitaxel (PTX), and a hydrophilic poly(ethylene glycol) (PEG) shell increases the solubility of the nGr drug delivery system. Importantly, the polymer coating mediates the interaction of nGr with U‐138 glioblastoma cells and decreases cytotoxicity compared with pristine untreated nGr. PLA‐PEG‐coated nGr is also able to encapsulate PTX at 4.15 wt% and sustains prolonged PTX release for at least 19 d. PTX‐loaded nGr‐PLA‐PEGs are shown to kill up to 20% of U‐138 glioblastoma cells in vitro. Furthermore, nGr‐PLA‐PEG and CNT‐PLA‐PEG, two carbon nanomaterials with different shapes, are able to kill U‐138 in vitro as well as free PTX at significantly lower doses of drug. Finally, in vivo biodistribution of nGr‐PLA‐PEG shows accumulation of nGr in intracranial U‐138 glioblastoma xenografts and organs of the reticuloendothelial system.     

Three‐dimensional coherent diffractive imaging on non‐periodic specimens at the ESRF beamline ID10

The progress of tomographic coherent diffractive imaging with hard X‐rays at the ID10 beamline of the European Synchrotron Radiation Facility is presented. The performance of the instrument is demonstrated by imaging a cluster of Fe₂P magnetic nanorods at 59 nm 3D resolution by phasing a diffraction volume measured at 8 keV photon energy. The result obtained shows progress in three‐dimensional imaging of non‐crystalline samples in air with hard X‐rays.     

Drug‐Conjugation Induced Self‐Assembly of Feather Keratin‐Based Prodrug for Tumor Intracellular Reduction Triggered Drug Delivery

As a kind of natural protein, keratin is widely investigated in the biomedical field. Here, for the first time, a keratin‐based prodrug (PK‐SS‐D) is designed for tumor intracellular reduction triggered drug delivery, by conjugating doxorubicin (DOX) onto poly(ethylene glycol) modified keratin (PEGylated keratin, PK) with a bioreducible disulfide linkage. The protein‐drug conjugate prodrug, with a drug content of 20%, can self‐assemble into micelles with a mean hydrodynamic diameter of 175 nm and a narrow distribution. The in vitro controlled release profiles reveal the reduction triggered thiolated DOX (DOX‐SH) release behavior of the PK‐SS‐D micelles, with a cumulative drug release up to 52% within 10 d in the simulated tumor microenvironment in a sustained releasing mode, and a low drug leakage of 17% in the simulated normal physiological medium. The enhanced tumor growth inhibition of the proposed PK‐SS‐D prodrug micelles is revealed by the methyl tetrazolium (MTT) assays, although the released DOX‐SH prodrug possesses a lower tumor growth inhibition than DOX.     

Evaluation of Rod‐Shaped Nanoparticles as Carriers for Gene Delivery

Fabrication of nonspherical particles for gene delivery remains a major challenge. In this study, novel rod‐like nanoparticles are prepared for efficient gene delivery by self‐assembly of α‐cyclodextrin (α‐CD) and polyethylenimine‐methoxy poly(ethylene glycol) (PEI‐mPEG). The study reveals that the rod‐like PEI‐mPEG/α‐CD particles can bind DNA effectively and the resulting PEI‐mPEG/α‐CD/DNA complexes show over four times higher gene delivery capability than their spherical counterparts and PEI(25K) due to more efficient cellular uptake. Furthermore, the cytotoxicity of rod‐like PEI‐mPEG/α‐CD is about five times lower than that of the nanospheres, and 50 times lower than that of DNA/PEI(25K). These results indicate that shape is an important parameter for the design of gene delivery vectors.     

Gold‐Nanoparticle‐Assisted Self‐Assembly of Chemical Gradients with Tunable Sub‐50 nm Molecular Domains

A simple and efficient principle for nanopatterning with wide applicability in the sub‐50 nanometer regime is chemisorption of nanoparticles; at homogeneous substrates, particles carrying surface charge may spontaneously self‐organize due to the electrostatic repulsion between adjacent particles. Guided by this principle, a method is presented to design, self‐assemble, and chemically functionalize gradient nanopatterns where the size of molecular domains can be tuned to match the level corresponding to single protein binding events. To modulate the binding of negatively charged gold nanoparticles both locally (<100 nm) and globally (>100 μm) onto a single modified gold substrate, ion diffusion is used to achieve spatial control of the particles’ mutual electrostatic interactions. By subsequent tailoring of different molecules to surface‐immobilized particles and the void areas surrounding them, nanopatterns are obtained with variable chemical domains along the gradient surface. Fimbriated Escherichia coli bacteria are bound to gradient nanopatterns with similar molecular composition and macroscopic contact angle, but different sizes of nanoscopic presentation of adhesive (hydrophobic) and repellent poly(ethylene) glycol (PEG) domains. It is shown that small hydrophobic domains, similar in size to the diameter of the bacterial fimbriae, supported firmly attached bacteria resembling catch‐bond binding, whereas a high number of loosely adhered bacteria are observed on larger hydrophobic domains.     

Structure and Stability of PEG‐ and Mixed PEG‐Layer‐Coated Nanoparticles at High Particle Concentrations Studied In Situ by Small‐Angle X‐Ray Scattering

Ligand‐layer structure and stability of gold nanoparticles (AuNP) coated with α‐methoxypoly(ethylene glycol)‐ω‐(11‐mercaptoundecanoate) (PEGMUA) layers and mixed layers of PEGMUA and 11‐mercaptoundecanoic acid (MUA) at high AuNP concentrations are studied in situ by small‐angle X‐ray scattering (SAXS). The thickness of the ligand layer is modified by the molecular weight of the PEG‐ligands (2 and 5 kDa), and the PEG‐grafting density is decreased by coadsorption of MUA. The response of the conjugates to a pressure of up to 4 kbar is probed. The results indicate strongly hydrated PEG layers at high grafting densities. The stability of the mixed ligand‐layer conjugates is lower. This is most probably due to enhanced interparticle PEG–PEG interactions at lower grafting densities. The presented study demonstrates that a detailed structural characterization of polymer ligand layers in situ and in response to external stimuli is possible with SAXS.     

Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers

Solvent-induced aggregation and its effect on the intrinsic emission properties of amine, hydroxy and carboxylate terminated, poly(amidoamine) (PAMAM) dendrimers have been investigated in glycerol, ethylene glycol, methanol, ethylene diamine and water. Altering the solvent medium induces remarkable changes in the intrinsic emission properties of the PAMAM dendrimers at identical concentration. Upon excitation at 370 nm, amine terminated PAMAM dendrimer exhibits an intense emission at 470 nm in glycerol, ethylene glycol as well as glycerol-water mixtures. Conversely, weak luminescence is observed for hydroxy and carboxylate terminated PAMAM dendrimers in the same solvent systems. When the solvent is changed to ethylene diamine, hydroxy terminated PAMAM exhibits intense blue emission at 425 nm. While the emission intensity is varied when the solvent milieu is changed, excited state lifetime values of PAMAM dendrimers remain independent of the solvent used. UV-visible absorption and dynamic light scattering (DLS) experiments confirm the formation of solvent-controlled dendrimer aggregates in the systems. Comparison of the fluorescence and DLS data reveals that the size distribution of the dendrimer aggregates in each solvent system is distinct, which control the intrinsic emission intensity from PAMAM dendrimers. The experimental results suggest that intrinsic emission intensity from PAMAM dendrimers can be regulated by proper selection of solvents at neutral conditions and room temperature.