π-Stacking Stopper-Macrocycle Stabilized Dynamically Interlocked [2]Rotaxanes.

The synthesis of mechanically interlocked molecules is valuable due to their unique topologies. With π-stacking intercomponent interaction, e.g., phenanthroline and anthracene, novel [2]rotaxanes have been synthesized by dynamic imine clipping reaction. Their X-ray crystal structures indicate the π-stackings between the anthracene moiety (stopper) on the thread and the (hetero)aromatic rings at the macrocycle of the rotaxanes. Moreover, the length of glycol chains affects the extra π-stacking intercomponent interactions between the phenyl groups and the dimethoxy phenyl groups on the thread. Dynamic combinatorial library has shown at best 84% distribution of anthracene-threaded phenanthroline-based rotaxane, coinciding with the crystallography in that the additional π-stacking intercomponent interactions could increase the thermodynamic stability and selectivity of the rotaxanes.

Mechanism for the Cellular Uptake of Targeted Gold Nanorods of Defined Aspect Ratios.

Biomedical applications of non-spherical nanoparticles such as photothermal therapy and molecular imaging require their efficient intracellular delivery, yet reported details on their interactions with the cell remain inconsistent. Here, the effects of nanoparticle geometry and receptor targeting on the cellular uptake and intracellular trafficking are systematically explored by using C166 (mouse endothelial) cells and gold nanoparticles of four different aspect ratios (ARs) from 1 to 7. When coated with poly(ethylene glycol) strands, the cellular uptake of untargeted nanoparticles monotonically decreases with AR. Next, gold nanoparticles are functionalized with DNA oligonucleotides to target Class A scavenger receptors expressed by C166 cells. Intriguingly, cellular uptake is maximized at a particular AR: shorter nanorods (AR = 2) enter C166 cells more than nanospheres (AR = 1) and longer nanorods (AR = 4 or 7). Strikingly, long targeted nanorods align to the cell membrane in a near-parallel manner followed by rotating by ≈90° to enter the cell via a caveolae-mediated pathway. Upon cellular entry, targeted nanorods of all ARs predominantly traffic to the late endosome without progressing to the lysosome. The studies yield important materials design rules for drug delivery carriers based on targeted, anisotropic nanoparticles.

Noble Metal-Iron Oxide Hybrid Nanomaterials: Emerging Applications.

This account provides an overview of current research activities that focus on the synthesis and applications of nanomaterials from noble metal (e.g., Au, Ag, Pd) and iron oxide (Fe3O4) hybrids. An introduction to the synthetic strategies that have been developed for generating M-Fe3O4 nanomaterials with different novel structures is presented. Surface functionalization and bioconjugation of these hybrid nanoparticles and nanocomposites are also reviewed. The utilization of the advantageous properties of both noble metals and iron oxide for a variety of applications, such as theranostics, gene delivery, biosensing, cell sorting, bioseparation, and catalysis, is discussed and highlighted. Finally, future trends and perspectives of these sophisticated nanocomposites are outlined. The fundamental requirements underpinning the effective preparation of M-Fex Oy hybrid nanomaterials shed light on the future development of heterogeneous catalysts, nanotheranostics, nanomedicines, and other chemical technologies.

High Performance Photoluminescent Carbon Dots for In Vitro and In Vivo Bioimaging: Effect of Nitrogen Doping Ratios.

Photoluminescent carbon dots (CDs) have received ever-increasing attention in the application of optical bioimaging because of their low toxicity, tunable fluorescent properties, and ultracompact size. We report for the first time on enhanced photoluminescence (PL) performance influenced by structure effects among the various types of nitrogen doped (N-doped) PL CDs. These CDs were facilely synthesized from condensation carbonization of linear polyethylenic amine (PEA) analogues and citric acid (CA) of different ratios. Detailed structural and property studies demonstrated that either the structures or the molar ratio of PEAs altered the PL properties of the CDs. The content of conjugated π-domains with C═N in the carbon backbone was correlated with their PL Quantum Yield (QY) (up to 69%). The hybridization between the surface/molecule state and the carbon backbone synergistically affected the chemical/physical properties. Also, long-chain polyethylenic amine (PEA) molecule-doped CDs exhibit increasing photostability, but at the expense of PL efficiency, proving that the PL emission of high QY CDs arise not only from the sp(2)/sp(3) carbon core and surface passivation of CDs, but also from the molecular fluorophores integrated in the CDs. In vitro and in vivo bioimaging of these N-doped CDs showed strong photoluminescence signals. Good biocompatibility demonstrates their potential feasibility for bioimaging applications. In addition, the overall size profile of the as-prepared CDs is comparable to the average size of capillary pores in normal living tissues (∼5 nm). Our study provides valuable insights into the effects of the PEA doping ratios on photoluminescence efficiency, biocompatibility, cellular uptake, and optical bioimaging of CDs.

Revisiting the formation and tunable dissociation of a [2]pseudorotaxane formed by slippage approach.

A new [2]pseudorotaxane DB24C8⊃1-H · PF6 with dibenzo[24]crown-8 (DB24C8) crown ether-dibenzylammonium (1-H · PF6) binding which was formed by slippage approach at different solvents and temperature, had been isolated and characterized by NMR spectroscopy and mass spectrometry. The [2]pseudorotaxane DB24C8⊃1-H · PF6 was stable at room temperature. The dissociation rate of [2]pseudorotaxane DB24C8⊃1-H · PF6 could be tuned by using different stimuli such as triethylamine (TEA)/diisopropylethylamine (DIPEA) and dimethyl sulfoxide (DMSO). In particular, the dissociation of [2]pseudorotaxane DB24C8⊃1-H · PF6 by an excess of TEA/DIPEA base mixture possessed a long and sustained, complete dissociation over 60 days. Other stimuli by DMSO possessed a relatively fast dissociation over 24 h.

Nanoparticle-DNA-polymer composites for hepatocellular carcinoma cell labeling, sensing, and magnetic resonance imaging.

This paper describes comparative studies and protocols in (1) self-assembling of ultrasmall superparamagnetic iron oxide nanoparticle (NP), circular plasmid DNA, and branched polyethylenimine (PEI) composites; (2) magnetofection; (3) gene delivery, (4) magnetic resonance imaging (MRI), and (5) cytotoxicity of the composites toward hepatocellular carcinoma HepG2 cells.

In vivo chemoembolization and magnetic resonance imaging of liver tumors by using iron oxide nanoshell/doxorubicin/poly(vinyl alcohol) hybrid composites.

A hybrid composite made up of superparamagnetic iron oxide nanoshells encapsulating the anticancer drug doxorubicin and bound together by poly(vinyl alcohol) was developed. Transcatheter arterial delivery in an in vivo liver tumor model led to embolization of the liver tumor blood vessels. Embolization was followed by disassembly of the composite. The nanoshells were then able to pass through the leaky tumor vasculature into the tumor tissue, thereby leading to slow and sustained release of the drug. As well as being relatively noncytotoxic, the composite was responsive to magnetic resonance imaging, thus making it a potentially useful theranostic agent.

Janus and Amphiphilic MoS2 2D Sheets for Surface-Directed Orientational Assemblies toward Ex Vivo Dual Substrate Release.

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight (MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

Gold and iron oxide hybrid nanocomposite materials.

This critical review provides an overview of current research activities that focused on the synthesis and application of multi-functional gold and iron oxide (Au-Fe(x)O(y)) hybrid nanoparticles and nanocomposites. An introduction of synthetic strategies that have been developed for generating Au-Fe(x)O(y) nanocomposites with different nanostructures is presented. Surface functionalisation and bioconjugation of these hybrid nanoparticles and nanocomposites are also reviewed. A variety of applications such as theranostics, gene delivery, biosensing, cell sorting, bio-separation, and catalysis is discussed and highlighted. Finally, future trends and perspectives of these sophisticated nanocomposites are outlined. Underpinning the fundamental requirements for effectively forming Au-Fe(x)O(y) hybrid nanocomposite materials would shed light on future development of nanotheranostics, nanomedicines, and chemical technologies. It would be interesting to investigate such multi-component composite nanomaterials with different novel morphologies in the near future to advance chemistry, biology, medicine, and engineering multi-disciplinary research (120 references).

NIR-induced improvement of catalytic activity and antibacterial performance over AuAg nanorods in Rambutan-like Fe3O4@AgAu@PDA magnetic nanospheres.

Pathogenic bacteria and difficult-to-degrade pollutants in water have been serious problems that always plague people. Therefore, finding a "one stone-two birds" method that can quickly catalyze the degradation of pollutants and show effective antibacterial behavior become an urgent requirement. This work reports a facile one-step strategy for fabricating a Rambutan-like Fe3O4@AgAu@PDA (Fe3O4@AgAu@Polydopamine) core/shell nanosphere with both catalytic and antibacterial activities which can be critically improved by externally applying an NIR laser irradiation (NIR, 808 nm) and a rotating magnetic field. Typically, the Rambutan-like Fe3O4@AgAu@PDA nanosphere have a rather rough surface due to the AuAg bimetallic nanorods sandwiched between the Fe3O4 core and the PDA shell. Owing to the penetrated PDA shell, AgAu nanorods show high and magnetically recyclable photothermal-enhanced catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol and they can also be applied to initiate TMB oxidation under the help of NIR heating condition. Moreover, Fe3O4@AgAu@PDA shows a moderate antibacterial activity due to the weak release of Ag+. Under applying a rotating external magnetic field, the rough-surface Fe3O4@AgAu@PDA nanospheres produce a controllable magnetolytic force on the bacterial due to their good affinity. As a result, the Fe3O4@AgAu@PDA nanospheres show a "magnetolytic-photothermal-Ag+" synergistic antibacterial behavior against E. coli and S. aureus.

One-Pot Preparation of Cetylpyridinium Chloride-Containing Nanoparticles for Biofilm Eradication.

Quaternary ammonium compounds (QACs) have been widely used due to their excellent antimicrobial activity. However, using the technology where nanomaterials are employed as drug carriers to deliver QAC drugs has not been fully explored. In this study, mesoporous silica nanoparticles (MSNs) with short rod morphology were synthesized in a one-pot reaction using an antiseptic drug cetylpyridinium chloride (CPC). CPC-MSN were characterized via various methods and tested against three bacterial species (Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis), which are associated with oral infections, caries, and endodontic pathology. The nanoparticle delivery system used in this study prolonged the release of CPC. The manufactured CPC-MSN effectively killed the tested bacteria within the biofilm, and their size allowed them to penetrate into dentinal tubules. This CPC-MSN nanoparticle delivery system demonstrates potential for applications in dental materials.

Wearable Safeguarding Leather Composite with Excellent Sensing, Thermal Management, and Electromagnetic Interference Shielding.

This work illustrates a "soft-toughness" coupling design method to integrate the shear stiffening gel (SSG), natural leather, and nonwoven fabrics (NWF) for preparing leather/MXene/SSG/NWF (LMSN) composite with high anti-impact protecting, piezoresistive sensing, electromagnetic interference (EMI) shielding, and human thermal management performance. Owing to the porous fiber structure of the leather, the MXene nanosheets can penetrate leather to construct a stable 3D conductive network; thus both the LM and LMSN composites exhibit superior conductivity, high Joule heating temperature, and an efficient EMI shielding effectiveness. Due to the excellent energy absorption of the SSG, the LMSN composites possess a huge force-buffering (about 65.5%), superior energy dissipation (above 50%), and a high limit penetration velocity of 91 m s-1 , showing extraordinary anti-impact performance. Interestingly, LMSN composites possess an unconventional opposite sensing behavior to piezoresistive sensing (resistance reduction) and impact stimulation (resistance growing), thus they can distinguish the low and high energy stimulus. Ultimately, a soft protective vest with thermal management and impact monitoring performance is further fabricated, and it shows a typical wireless impact-sensing performance. This method is expected to have broad application potential in the next-generation wearable electronic devices for human safeguarding.

Size-dependent magnetomechanically enhanced photothermal antibacterial effect of Fe3O4@Au/PDA nanodurian.

The global health crisis of bacterial resistance to antibiotics requires innovative antibacterial strategies. One promising solution is the exploitation of multifunctional nanoplatforms based on non-resistant antibacterial mechanisms. This work reports a novel Fe3O4@Au/polydopamine (PDA) nanodurian with excellent photothermal-magnetomechanic synergistic antibacterial effects. The one-step formed Au/PDA hybrid shell provides good photothermal properties and spiky surfaces for enhanced magnetomechanic effects. Upon near-infrared (NIR) irradiation, the Fe3O4@Au/PDA nanodurian (200 µg mL-1) achieved nearly 100% antibacterial effect against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The efficiency of photothermal antimicrobial activity was further enhanced by the application of a rotating magnetic field (RMF), with the sterilization efficiency being increased by up to more than a half compared to the action alone. Interestingly, the size of the nanodurian has a significant impact on the synergistic sterilization effect, with larger particles showing a superior performance due to stronger chain-like structures in the magnetic field. Finally, the Fe3O4@Au/PDA nanodurian also demonstrates effective biofilm removal, with larger particles exhibiting the best eradication effect under the photothermal-magnetomechanic treatment. Overall, this magnetic field enhanced photothermal antibacterial strategy provides a promising broad-spectrum antimicrobial solution to combat bacterial infections. Thus, it possesses great potential in future nanomedicine and pollution treatment.

A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses.

HYPOTHESIS: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare. EXPERIMENTS: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs. FINDINGS: The in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1ß. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer.

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 µM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.

Citrate-Coated Magnetic Polyethyleneimine Composites for Plasmid DNA Delivery into Glioblastoma.

Several ternary composites that are based on branched polyethyleneimine (bPEI 25 kDa, polydispersity 2.5, 0.1 or 0.2 ng), citrate-coated ultrasmall superparamagnetic iron oxide nanoparticles (citrate-NPs, 8-10 nm, 0.1, 1.0, or 2.5 µg), and reporter circular plasmid DNA pEGFP-C1 or pRL-CMV (pDNA 0.5 µg) were studied for optimization of the best composite for transfection into glioblastoma U87MG or U138MG cells. The efficiency in terms of citrate-NP and plasmid DNA gene delivery with the ternary composites could be altered by tuning the bPEI/citrate-NP ratios in the polymer composites, which were characterized by Prussian blue staining, in vitro magnetic resonance imaging as well as green fluorescence protein and luciferase expression. Among the composites prepared, 0.2 ng bPEI/0.5 µg pDNA/1.0 µg citrate-NP ternary composite possessed the best cellular uptake efficiency. Composite comprising 0.1 ng bPEI/0.5 µg pDNA/0.1 µg citrate-NP gave the optimal efficiency for the cellular uptake of the two plasmid DNAs to the nucleus. The best working bPEI concentration range should not exceed 0.2 ng/well to achieve a relatively low cytotoxicity.

Low-intensity pulsed ultrasound increases cellular uptake of superparamagnetic iron oxide nanomaterial: results from human osteosarcoma cell line U2OS.

PURPOSE: To determine whether low-intensity pulsed ultrasound (LIPUS) is able to facilitate the uptake of a superparamagnetic iron oxide (SPIO) nanomaterial by cells that do not express high endocytosis capacity. MATERIALS AND METHODS: The human osteosarcoma cell line U2OS and a silica-coated SPIO functionalized peripherally with amines groups (overall diameter 8 nm) were used in this study. Adherent U2OS cells were labeled with SPIO by incubating with culture media containing the SPIO at 4.5 microg[Fe]/mL. LIPUS with the same parameters as those used in clinical application to accelerate bone fracture healing (1.5 MHz, duty cycle 1:4, spatial-average temporal-average intensity 30 mW/cm(2)) was applied to the cells at the beginning of the labeling process for 0, 0.5, 1, or 3 hours. The total incubation time with SPIO was 12 hours. SPIO labeling efficiency was evaluated with Prussian blue staining and a blueness measurement method, and magnetic resonance imaging (MRI) of cell pellets via measuring areas of SPIO-induced signal void. RESULTS: Both Prussian blue staining and in vitro MRI demonstrated that LIPUS application increased the SPIO nanomaterial labeling efficiency for U2OS cells in an exposure-duration-dependent manner. CONCLUSION: This study is a "proof of concept" that LIPUS can facilitate the cellular take-up of SPIO nanomaterial.

Self-assembly, stability quantification, controlled molecular switching, and sensing properties of an anthracene-containing dynamic [2]rotaxane.

The preparation of a novel anthracene-containing dynamic [2]rotaxane by a templating self-assembly process between a diamine and a dialdehyde to form a [24]crown-8 macrocyclic diimine, in the presence of a dumbbell containing a secondary dialkylammonium ion center as the template, which has been exploited for its sensing properties. By appealing to the ability of the anthracene ring system--one of the two stoppers associated with the dumbbell--to act as a fluorescent probe, the fluorescence and fluorescence-quenching nature of the dynamic rotaxane in an equilibrium mixture has been investigated and quantified in the presence of external stimuli such as water, acids, salts, and an amine. The stability, as expressed by the hydrolysis of the dynamic rotaxane has been monitored by following: (i) the anthracene fluorescence and (ii) the movements of the signals in the (1)H NMR spectra. The rate of hydrolysis (t(1/2) = 6.9 min) of the dynamic rotaxane in the presence of a small amount (1 equiv.) of acid was found to be very much faster than when the hydrolysis was carried out with a large amount (>100 equiv.) of water, when t(1/2) > 140 min. Furthermore, it has been established that the anthracene fluorescence of the dynamic rotaxane rises with an increasing amount of acid. Two acid sensors have been identified with different operating modes-namely, logarithmic and linear. The combination of different inputs involving water, acids, salts and an amine leads to different fluorescence outputs from the dynamic rotaxane, hence, producing a prototype for expressing molecular logic.

The stability of imine-containing dynamic [2]rotaxanes to hydrolysis.

Large amounts (>100 mol equivalents) of water are required to effect by hydrolysis the partial disassembly of the rings from the dumbbell components of two dynamic [2]rotaxanes. The two dynamic [2]rotaxanes are comprised of [24]crown-8 rings-each of which incorporate two imine bonds-encircling a dumbbell component composed of a dibenzylammonium ion in which each of the two benzyl substituents carries two methoxyl groups attached to their 3- and 5-positions. A mechanism for the partial disassembly of the two dynamic [2]rotaxanes, involving the cleavage of the kinetically labile imine bonds by water molecules, is proposed. The most important experimental observation to be noted is the fact that the hydrolysis of the macrocyclic diimines, associated with the templating -CH(2)NH(2)(+)CH(2)-centres in the middle of their dumbbells, turns out to be an uphill task to perform in the face of the molecular recognition provided by strong [N(+)-HO] hydrogen bonds and weaker, yet not insignificant, [C-HO] interactions. The dynamic nature of the imine bond formation and hydrolysis is such that the acyclic components produced during hydrolysis of the imine bonds can be enticed to cyclise once again around the -CH(2)NH(2)(+)CH(2)-template, affording the [2]rotaxanes. The reluctance of imine bonds, present in substantial numbers in larger molecular and extended structures, is significant when it comes to exercising dynamic chemistry in compounds where multiple imine bonds are present.

Selective detection of sulfide in human lung cancer cells with a blue-fluorescent "ON-OFF-ON" benzimidazole-based chemosensor ensemble.

A completely water-soluble, high quantum yield blue-fluorescent benzimidazole derivative (AQ), containing a rigid benzimidazole-thiophene structure, was synthesized. Among 21 metal ions, the fluorescence of AQ was selectively turned off by Cu2+ to form an AQ-Cu2+ ensemble. Thereafter, the fluorescence of the AQ-Cu2+ ensemble was turned on by sulfide (S2-) with high selectivity and sensitivity in pure water solution. In comparison with AQ-Ag+ and AQ-Hg2+ ensembles, AQ-Cu2+ was the only ensemble that was capable of detecting a sulfide anion. Also, the fluorescence intensity of AQ was linearly proportional to the concentration of Cu2+ and S2-. Both Cu2+ and S2- were detected within a minute in vitro. Moreover, AQ worked best in the pH range of 5-10 and had a limit of detection of 50 nM and 354 nM for Cu2+ and S2- respectively. It was employed for the detection of sulfide in human lung cancer A549 cells with low cytotoxicity.