Ordered Networks of Gold Nanoparticles Crosslinked by Dithiol‐Oligomers

Controlled aggregation of nanoparticles into superlattices is a grand challenge in material science, where ligand based self‐assembly is the dominant route. Here, the self‐assembly of gold nanoparticles (AuNPs) that are crosslinked by water soluble oligo‐(ethylene glycol)‐dithiol (oEG‐dithiol) is reported and their 3D structure by small angle X‐ray scattering is determined. Surprisingly, a narrow region is found in the parameter space of dithiol linker‐length and nanoparticle size for which the crosslinked networks form short‐ranged FCC crystals. Using geometrical considerations and numerical simulations, the stability of the formed lattices is evaluated as a function of dithiol length and the number of connected nearest‐neighbors, and a phase diagram of superlattice formation is provided. Identifying the narrow parameter space that allows crystallization facilitates focused exploration of linker chemical composition and medium conditions such as thermal annealing, pH, and added solutes that may lead to superior and more robust crystals.     

Self‐Assembly of Spherical or Rod‐Shaped Magnetic Nanocrystals onto Curved Substrates Governed by the Radius of Curvature

The way the assembly of colloidal nanostructures into heterostructures takes place substantially affects their physicochemical properties and performance. The layer‐by‐layer self‐assembly has shown in this regard a huge ability to drive nanomaterials onto curved substrates. Hindering the clustering to improve the distribution and allocation of nanoparticles on these assemblies can be partially controlled by geometric frustration, herein demonstrated driving magnetic nanocrystals with different morphology onto spherical substrates of tuned curvature.     

Rod‐Shaped Drug Particles for Cancer Therapy: The Importance of Particle Size and Participation of Caveolae Pathway

It is disclosed how the sizes of rod‐shaped paclitaxel‐nanosuspensions (PTX‐Ns) that are less than 500 nm affect their in vitro and in vivo performances. A size reduction from 500 to 160 nm enhances the cellular uptake and subsequent cytotoxicity, due to the participation of caveolae‐mediated endocytosis; moreover, the ability of the PTX‐Ns to penetrate tumors is well correlated with the extent to which the caveolae pathway participates in cellular uptake, as their ability to target caveolae is markedly promoted as their size decreased to 160 nm. Also, the size reduction markedly alters the in vivo performance and tumor targeting. It is disclosed that via enhanced tumor penetration and retention but not simply increased tumor accumulation, size reduction of PTX‐Ns results in significant improvement in antitumor activities. Overall, this study highlights the importance of the size of the PTX‐Ns and the participation of caveolae‐mediated endocytosis in controlling their biological functions and will assist in the design and optimization of new nanosuspension formulations for disease therapy.     

Colloidal Flower‐Shaped Iron Oxide Nanoparticles: Synthesis Strategies and Coatings

The assembly of magnetic cores into regular structures may notably influence the properties displayed by a magnetic colloid. Here, key synthesis parameters driving the self‐assembly process capable of organizing colloidal magnetic cores into highly regular and reproducible multi‐core nanoparticles are determined. In addition, a self‐consistent picture that explains the collective magnetic properties exhibited by these complex assemblies is achieved through structural, colloidal, and magnetic means. For this purpose, different strategies to obtain flower‐shaped iron oxide assemblies in the size range 25–100 nm are examined. The routes are based on the partial oxidation of Fe(OH)₂, polyol‐mediated synthesis or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran, citric acid, or alternatively embedded in polystyrene and their long‐term stability is assessed. The core size is measured, calculated, and modeled using both structural and magnetic means, while the Debye model and multi‐core extended model are used to study interparticle interactions. This is the first step toward standardized protocols of synthesis and characterization of flower‐shaped nanoparticles.     

Nanoparticles Engineering for Lithium‐Ion Batteries

Lithium‐ion batteries (LIBs) have been extensively investigated due to the ever‐increasing demand for new electrode materials for electric vehicles (EVs) and clean energy storage. A wide variety of nano/microstructured LIBs electrode materials are hitherto created via self‐assembly, ranging from 0D nanospheres; 1D nanorods, nanowires, or nanobelts; and 2D nanofilms to 3D nanorod array films. Nanoparticles can be utilized to build up integrated architectures. Understanding of nanoparticles’ self‐assembly may provide information about their organization into large aggregates through low‐cost, high‐efficiency, and large‐scale synthesis. Here, the focus is on the recent advances in preparing hierarchically nano/microstructured electrode materials via self‐assembly. The hierarchical electrode materials are assembled from single component, binary to multicomponent building blocks via different driving forces including diverse chemical bonds and non‐covalent interactions. It is expected that nanoparticle engineering by high‐efficient self‐assembly process will impact the development of high‐performance electrode materials and high‐performance LIBs or other rechargeable batteries.     

Preparation,Characterization and Optimization of Egg Albumin Nanoparticles as Low Molecular‐Weight Drug Delivery Vehicle

Protein nanoparticles have been recognized as carriers to deliver low molecular‐weight drugs, anticancer drug, DNA, vaccines, oligonucleotides, peptides and etc. The purpose of this research was preparation of Egg Albumin (EA) nanoparticle with suitable size/size distribution and good surface properties for drug delivery application based on simple coacervation method along with optimization of the nanoparticles by employing Taguchi method. Several synthesis parameters were examined to characterize their impacts on nanoparticle size and topography. These variables were including temperature, EA concentration, desolvating agent volume, pH value and agitation speed. In addition, size and morphology of prepared nanoparticles were analyzed by photon correlation spectroscopy (PCS) as well as atomic force microscopy (AFM). As result of Taguchi analysis in this research, desolvating agent volume and pH were most influencing factors on particle size. The minimum size of nanoparticles (～51 nm) were obtained at Temperature 55 °C, 30 mg/ml EA concentration, desolvating agent volume 50 ml, agitation speed of 500 rpm and pH 4. The mechanistic of optimum conditions for preparing protein nanoparticles from Egg Albumin for the first time and their characterization as delivering nano system are discussed.     

An Improved Method for Site‐Specific End Modification of Zeolite L for the Formation of Zeolite L and Gold Nanoparticle Self‐Assembled Structures

The ability to site‐selectively modify micro‐ and nanosized particles has allowed for directed self‐assembly in two and three dimensions. Site‐selective modification of particles can be a complicated task requiring the pre‐organization of particles or enhanced particle fabrication methods. The aluminum silicate, zeolite L has been reported to undergo site‐specific modification at the zeolite channel entrances, post‐fabrication in a solution‐based method. The process by which the channel entrances are site selectively modified is explored here. The preliminary step of charging the zeolite channels with aqueous acid allows for catalysis of covalent bond formation at the channel entrances. Three new end‐specific modification reagents are described based on silanol and silyl ether functional groups. These reagents are purified by column chromatography and characterized by¹H NMR spectroscopy and high resolution mass spectrometry (HRMS); they provide for reliable end modification of zeolites L. Preferential reactivity at the channel entrances is also observed. The utility of the approach is demonstrated by modifying zeolite L with adamantane at the channel entrances. Site‐specific self‐assembly with β‐cyclodextrin coated gold nanoparticles can be triggered with a chemical stimulus. The resulting multivalent host‐guest interactions give gold clustered nanoparticles at the ends of the micrometer‐sized zeolites.     

Self‐Assembled Fluorescent and Antibacterial GHK‐Cu Nanoparticles for Wound Healing Applications

GHK‐Cu is demonstrated with the abilities to improve wound healing, accelerate anti‐inflammatory activity, and repair DNA damage. However, the instability of the GHK‐Cu in biological fluids is always a big challenge for its long‐term and efficient function at the target site. Therefore, the self‐assembled GHK‐Cu nanoparticles (GHK‐Cu NPs) are investigated in this work to solve the instability issue. The crystalline nanostructure within the GHK‐Cu nanoparticles offers them visible and near‐infrared fluorescent properties. With the excellent self‐assembly performance, the antibacterial properties of GHK‐Cu NPs are demonstrated using E. coli and S. aureus. The L929 dermal fibroblast cells are utilized to prove the good biocompatibility and enhanced wound healing applications of GHK‐Cu NPs. This study could pave the way for the design and elaboration of a new class of fluorescent peptides with various biological functions in biomedical applications.     

Destabilization of Thiolated Gold Clusters for the Growth of Single‐Crystalline Gold Nanoparticles and Their Self‐Assembly for SERS Detection

Thiolate‐protected gold nanoclusters with high chemical stability are exploited extensively for fundamental research and utility in chosen applications. Here for the first time, the controlled destabilization of extraordinarily stable thiolated gold clusters for the growth of single‐crystalline gold nanoparticles (AuNPs) is demonstrated, which was achieved simply via the oxidation of surface‐protecting thiolates into disulfides by hydrogen peroxide under basic condition. By combining with our experimental observations over the entire destabilization and growth process, the new growth mechanism from clusters to AuNPs is revealed by density functional theory (DFT) calculations. It is found that the size of AuNPs decreases with the increase of hydrogen peroxide concentration due to the generation of more nuclei at the higher hydrogen peroxide concentrations. In addition, the preparation of AuNPs is tuned by changing the concentration of hydrogen peroxide, and they are self‐assembled into microspheres via an evaporation‐mediated process, which can induce strong plasmonic coupling between adjacent AuNPs for ultrasensitive surface‐enhanced Raman scattering detection. The present work demonstrates a facile route to functionalize and engineer AuNPs via controlling the reaction conditions and the ratio of precursors, and thus bring new possibilities for using more clusters as precursors to construct novel nano/microstructures for various applications.     

Self‐Assembly of Drug–Drug Conjugates as Drug Self‐Delivery System for Tumor‐Specific pH‐Triggered Release

An acid‐labile doxorubicin dimer (D‐DOX) is designed as drug–drug conjugate for tumor intracellular pH‐triggered release, by conjugating doxorubicin (DOX) with adipic acid dihydrazide (ADH). The dimer‐based surfactants modified with polyethylene glycol (PEG), DOX‐ADH‐DOX‐PEG or are synthesized by mono‐PEGylation and bi‐PEGylation, respectively. Then the prodrug nanoparticles are fabricated with different drug contents via dialyzing the mixture solution of D‐DOX and the PEGylated surfactants in dimethyl sulfoxide (DMSO) with different mass ratios against water. It is found that the smaller prodrug nanoparticles (142–163 nm) could be obtained with the mono‐PEGylated surfactant, than those of 157–225 nm with the bi‐PEGylated surfactant. Furthermore, the mono‐PEGylated surfactant results in a higher drug content of 51% due to their lower PEG contents. All prodrug nanoparticles could release DOX completely within 36 h at pH 5.0, with the premature drug leakage of less than 10% at pH 7.4. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays demonstrate the proposed drug self‐delivery system possessed an enhanced anticancer efficacy against HepG2 cells than the free DOX.     

Phosphonated Polyethylenimine‐Coated Nanoparticles: Size‐ and Zeta‐Potential‐Adjustable Nanomaterials

Novel partially phosphonated polyethylenimine polymers are developed in order to control the modification of nanoparticle (NP) surfaces. This polymer is built by an accessible one‐step process. The numerous phosphonate functions assume both a strong covalent anchoring on metal oxide NPs and a modulation of electric charges, while amino groups are associated with dispersion preservation and subsequent biofunctionalization. The zwitterionic nanomaterials obtained display a good stability toward pH and ionic strength. According to the selected percentage of phosphonation and the polymer size, zeta potential, and diameter of the particles are controlled.     

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.     

Human‐Serum‐Albumin‐Coated Prussian Blue Nanoparticles as pH‐/Thermotriggered Drug‐Delivery Vehicles for Cancer Thermochemotherapy

Constructing novel multimodal antitumor therapeutic nanoagents has attracted tremendous recent attention. In this work, a new drug‐delivery vehicle based on human‐serum‐albumin (HSA)‐coated Prussian blue nanoparticles (PB NPs) is synthesized. It is demonstrated that doxorubicin (DOX)/HSA is successfully loaded after in situ polymerization of dopamine onto PB NPs, and the PB@PDA/DOX/HSA NPs are highly compatible and stable in various physiological solutions. The NPs possess strong near‐infrared (NIR) absorbance, and excellent capability and stability of photothermal conversion for highly efficient photothermal therapy applications. Furthermore, a bimodal on‐demand drug release sensitively triggered by pH or NIR irradiation has been realized, resulting in a significant chemotherapeutic effect due to the preferential uptake and internalization of the NPs by cancer cells. Importantly, the thermochemotherapy efficacy of the NPs has been examined by a cell viability assay, revealing a remarkably superior synergistic anticancer effect over either monotherapy. Such multifunctional drug‐delivery systems composed of approved materials may have promising biomedical applications for antitumor therapy.     

Biodegradable Passion Fruit‐Like Nano‐Architectures as Carriers for Cisplatin Prodrug

Accumulation of inorganic nanostructures in the excretory system organs increases their likelihood of toxicity and interference with common medical diagnoses. Thus, one of the major concerns regarding their clinical translation is related to their persistence in organisms. Here the authors demonstrate that nano‐architectures composed by hollow silica nanocapsules embedding arrays of ultrasmall gold nanoparticles undergo biodegradation in cellular environment affording small, potentially clearable building blocks. Furthermore, the authors present their exploitation in glutathione‐triggered release of covalently loaded cisplatin prodrug. This endogenously triggered release leads to high cytotoxicity to human pancreatic carcinoma cells, setting the way for promising applications to synergistic dual chemo/radio‐therapy and radio‐imaging.     

DTT–Au NCs Interact with DNA to Form Raspberry‐Like Particles

Noble metal nanoclusters (NCs) have emerged as intriguing nanomaterials with widespread interest. Previously, it was shown that dithiothreitol (DTT)‐conjugated gold nanoclusters (Au NCs) respond to copper ions in aqueous solution. Here, it is shown that these DTT–Au NCs can interact with DNA by forming raspberry‐like particles. The raspberry‐like structures protect the capped DNA from enzymatic attack and show excellent biocompatibility. Moreover, these supramolecular complexes cross the plasma membrane of yeast cells and express green fluorescent protein encoded by the DNA, suggesting that DTT–Au NCs can serve as an efficient carrier for gene delivery.     

Real‐time three‐dimensional single‐particle tracking spectroscopy for complex systems

Complex systems are characterized by dynamical processes spread over multiple time and length scales. At a given instant, these systems can display spatial heterogeneities in which the local physical and chemical properties are nonuniform, depending on the location. They can also exhibit dynamical heterogeneities in which the local dynamical characteristics vary with time. These types of systems pose unique experimental challenges for their characterization and test of theoretical ideas. Recently, real‐time three‐dimensional (3D) single‐particle tracking spectroscopy has been developed to address these kinds of problems. With this approach, in principle, one can follow how a system evolves spatially as well as temporally. This article attempts to provide an introduction to this promising new technique by discussing the aims of studying a complex system and recent experimental advances towards this goal.