Janus Nanoparticle Emulsions as Chiral Nanoreactors for Enantiomerically Selective Ligand Exchange

Janus nanoparticles capped with a hydrophobic and hydrophilic hemisphere of mercapto ligands can self‐assemble into hollow, emulsion‐like nanostructures in controlled media. As the nanoparticle emulsions are chiroptically active exhibiting a plasmonic circular dichroism absorption in the visible range, they can be exploited as a unique chiral nanoreactor by selective encapsulation of d ‐enantiomer into the water phase of the water‐in‐oil emulsions for directional functionalization of the nanoparticles and endow the resulting nanoparticles with select chirality. This is demonstrated in the present study with gold Janus nanoparticles functionalized with (hydrophobic) hexanethiolates and (hydrophilic) 3‐mercapto‐1,2‐propandiol, and d ,l ‐cysteine is used as the molecular probe. Experimental results demonstrate that d ‐cysteine is the preferred enantiomers entrapped within the nanoparticle emulsions, where the ensuing ligand exchange reaction is initially confined to the hydrophilic face of the Janus nanoparticles. This suggests that with a deliberate control of the reaction time, chiral Janus nanoparticles can be readily prepared by ligand exchange reactions even with a racemic mixture of ligands.     

Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.     

Fluorescence Correlation Spectroscopy of Gold Nanoparticles

Diffusion dynamics of gold nanoparticles (GNPs) was studied by fluorescence correlation spectroscopy (FCS). The fluorescence was studied by exciting the particles by green laser (532 nm), which is far from longitudinal plasmon band of nanorods. Transmission electron microscope (TEM) and UV-Vis-NIR spectrometer were used to characterize the gold nanoparticles. Despite their low quantum yields, GNPs possess the native fluorescence. The excellent antiphotobleaching behavior of gold nanorods leads to prospects of using FCS for its detailed studies. Using FCS, dynamic information can be extracted from the fluorescence fluctuations in the system by autocorrelation function. Maximum entropy method (MEMFCS) was used to identify the number of distinct components present in the system. The particle sizes obtained from FCS were found to be higher (by few orders of magnitude) compared to TEM analysis. This might be due to the possible contributions from cetyltrimethyl ammonium bromide (CTAB) capping in the system.     

High‐Resolution Label‐Free Detection of Biocompatible Polymeric Nanoparticles in Cells

The design of efficient drug nanocarriers necessitates a deep understanding of their interaction with targeted cells. Polymeric poly(lactic acid) (PLA) or poly(d ,l ‐lactic‐co‐glycolic acid) nanoparticles (NPs) with sizes lower than 200 nm are among the most employed nanocarriers in drug delivery. Their detection inside cells requires appropriate labeling for high‐resolution imaging techniques, which unfortunately often alter their physicochemical properties and biological fate. Moreover, nowadays no high‐resolution method allows precise detection simultaneously to the identification of NPs chemical composition in cells, which is of outmost interest to gain insights on their fate. Here, this challenge is addressed by using an innovative atomic force microscope coupled with a tunable infrared laser source (nanoIR). NanoIR is used to unambiguously identify PLA NPs of around 170 nm with high resolution. A reliable, nondestructive, and direct method able to precisely locate and chemically characterize PLA NPs within a cell without the need of labeling is presented.     

Inkjet-Based Technology for Microencapsulation of Gold Nanoparticles within Biocompatible Hydrogels

Herein, an inkjet-based technology as a versatile high throughput methodology for the microencapsulation of gold nanoparticles (AuNPs) inside a biocompatible chitosan hydrogel is described. This continuous automated inkjet production approach generates 30 µm diameter polymeric microcapsules and offers a high rate of production and nanoparticle encapsulation efficiency of 14 nm diameter AuNPs, precise control of the microcapsule size, and ease of scale-up. The hybrid microcapsules demonstrate biocompatible cell-adhesion properties and resist degradation over a large range of pH, making them particularly relevant for a variety of potential health applications.     

Study of tryptophan assisted synthesis of gold nanoparticles by combining UV–Vis, fluorescence, and SERS spectroscopy

We developed a rapid and non-toxic method for the preparation of colloidal gold nanoparticles (GNPs) by using tryptophan (Trp) as reducing/stabilizing agent. We show that the temperature has a major influence on the kinetics of gold ion reduction and the crystal growth, higher temperatures favoring the synthesis of anisotropic nanoparticles (triangles and hexagons). The as-synthesized nanostructures were characterized by UV–Vis absorption spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), fluorescence, and surface-enhanced Raman scattering (SERS) spectroscopy. The UV–Vis measurements confirmed that temperature is a critical factor in the synthesis process, having a major effect on the shape of the synthesized GNPs. Moreover, fluorescence spectroscopy was able to monitor the quenching of the Trp fluorescence during the in situ synthesis of GNPs. Using Trp as molecular analyte to evaluate the SERS efficiency of as-prepared GNPs at different temperatures, we demonstrated that the Raman enhancement of the synthesized gold nanoplates is higher than that of the gold spherical nanoparticles.     

An anisotropic snowflake-like structural assembly of polymer-capped gold nanoparticles

Snowflake-like structural assembly of isotropic gold nanoparticles (GNPs) is reported. A modified polyamine method has been employed to synthesize positively charged GNPs in presence of a polymeric metaphosphate. This process yields fascinating dendritic self-assembled morphologies. Structural characterization revealed that there was aggregation of crystalline GNPs. The aggregates of GNPs formed in the initial stage of synthesis are assumed to act as the bulging seeds for final growth of complex morphologies at nanometer to micrometer length scale. Self-assembly of GNPs was found to be greatly influenced by the concentration of gold precursor. Diffusion limited aggregation of GNPs is suggested as the plausible mechanism for this nanoparticle self-organization process.     

Assembly of Gold Nanoparticles on Gold Nanorods Using Functionalized Poly(N‐isopropylacrylamide) as Polymeric “Glue”

A telechelic thermoresponsive polymer, α‐amino‐ω‐thiol‐poly(N‐isopropylacrylamide) (H₂N‐PNiPAM‐SH), is used as the polymeric glue to assemble gold nanoparticles (AuNPs) around gold nanorods (AuNRs) into a satellite structure. Prepared by reversible addition‐fragmentation chain transfer polymerization followed by hydrazinolysis, H₂N‐PNiPAM‐SH is able to interlink the two types of the gold building blocks with the thiol‐end grafting on AuNRs and the amine‐end coordinating on the AuNP surface. The density of the grafted AuNPs on AuNRs can be tuned by adjusting the molar ratio between AuNPs and AuNRs in the feed. The resulted satellite‐like assembly exhibits unique optical property that was responsive to temperature change.     

Video-frequency scanning transmission electron microscopy of moving gold nanoparticles in liquid

Immobilized gold nanoparticles were imaged in a liquid containing water and 50% glycerol with scanning transmission electron microscopy (STEM). The specimen was enclosed in a liquid compartment formed by two silicon microchips with electron transparent windows. A series of images was recorded at video frequency with a spatial resolution of 1.5nm. The nanoparticles detached from their support after imaging them for several seconds at a magnification of 250,000. Their movement was found to be much different than the movement of nanoparticles moving freely in liquid as described by Brownian Motion. The direction of motion was not random-the nanoparticles moved either in a preferred direction, or radially outwards from the center of the image. The displacement of the gold nanoparticles over time was three orders of magnitude smaller than expected on the basis of Brownian Motion. This finding implies that nanoscale objects of flexible structure or freely floating, including nanoparticles and biological objects, can be imaged with nanoscale resolution, as long as they are in close proximity to a solid support structure.     

A Correlative Analysis of Gold Nanoparticles Internalized by A549 Cells

Fluorescently labeled nanoparticles are widely used to investigate nanoparticle cell interactions by fluorescence microscopy. Owing to limited lateral and axial resolution, nanostructures (<100 nm) cannot be resolved by conventional light micro­scopy techniques. Especially after uptake into cells, a common fate of the fluorescence label and the particle core cannot be taken for granted. In this study, a correlative approach is presented to image fluorescently labeled gold nanoparticles inside whole cells by correlative light and electron microscopy (CLEM). This approach allows for detection of the fluorescently labeled particle shell as well as for the gold core in one sample. In this setup, A549 cells are exposed to 8 nm Atto 647N‐labeled gold nanoparticles (3.3 × 10⁹ particles mL^?1, 0.02 μg Au mL^?1) for 5 h and are subsequently imaged by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Eight fluorescence signals located at different intracellular positions are further analyzed by TEM. Five of the eight fluorescence spots are correlated with isolated or agglomerated gold nanoparticles. Three fluorescence signals could not be related to the presence of gold, indicating a loss of the particle shell.     

VEGFR-2 targeted cellular delivery of doxorubicin by gold nanoparticles for potential antiangiogenic therapy

We report a novel gold nanobioconjugate system that achieves targeted delivery of the small molecule drug doxorubicin to endothelial cells using anti-VEGFR-2 antibody conjugated gold nanoparticles (GNPs). The reported nanobioconjugate system combines the inherent ability of GNPs to undergo high levels of derivatization with the precision of antibody recognition of a cell surface antigen. Transmission electron microscopy (TEM) and surface-enhanced Raman spectroscopy (SERS) confirmed intracellular presence of the GNPs. Using a VEGFR-2 expressing cell line and a cell line that is negative for the receptor, in combination with competition assay we established the cell specific targeted delivery of the nanobioconjugate. The nanobioconjugate system described here may have potential drug delivery applications for antiangiogenic cancer therapy.     

Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles

The delivery of noscapine therapies directly to the site of the tumor would ultimately allow higher concentrations of the drug to be delivered, and prolong circulation time in vivo to enhance the therapeutic outcome of this drug. Therefore, we sought to design magnetic based polymeric nanoparticles for the site directed delivery of noscapine to invasive tumors. We synthesized Fe₃O₄ nanoparticles with an average size of 10±2.5 nm. These Fe₃O₄ NPs were used to prepare noscapine loaded magnetic polymeric nanoparticles (NMNP) with an average size of 252±6.3 nm. Fourier transform infrared (FT-IR) spectroscopy showed the encapsulation of noscapine on the surface of the polymer matrix. The encapsulation of the Fe₃O₄ NPs on the surface of the polymer was confirmed by elemental analysis. We studied the drug loading efficiency of polylactide acid (PLLA) and poly (l-lactide acid-co-gylocolide) (PLGA) polymeric systems of various molecular weights. Our findings revealed that the molecular weight of the polymer plays a crucial role in the capacity of the drug loading on the polymer surface. Using a constant amount of polymer and Fe₃O₄ NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.     

Novel Synthesis and Characterization of Doxycycline‐Loaded Gold Nanoparticles: The Golden Doxycycline for Antibacterial Applications

Doxycycline (DOXY) is a tetracycline antibiotic with a potent antibacterial activity against a wide variety of bacteria. One potential strategy to enhance the penetration and the antibacterial activity of antibiotics is the use of nanotechnology. In this work, an innovative synthesis of stable PEGylated‐gold nanoparticles (PEG‐AuNPs) loaded with DOXY is reported. As far as it is known, this is the first report on the combination of DOXY with AuNPs as polymeric complex. The obtained nanoparticles are fully characterized by transmission electron microscopy, dynamic light scattering, zeta‐potential, and UV–vis and Raman spectroscopy. The stability and sustained activity of the drug in nanoparticles is determined on a panel of Gram‐positive and Gram‐negative bacteria in comparison with the native form of the drug. This combined therapeutic agent restores the susceptibility of DOXY and shows an antibacterial activity against major human pathogens.     

Element‐specific microtomographic imaging of Drosophila brain stained with high‐Z probes

An application of X‐ray microtomography to the Drosophila adult brain stained with colloidal gold and a platinum compound is described. The transparency of biological tissue to hard X‐rays enables tomographic visualization of the three‐dimensional structure of tissue entrails. Each high‐Z element was visualized as a three‐dimensional structure from the difference absorption coefficient image at the corresponding L_III absorption edge. The cortex of the optic lobe was selectively visualized by the specific adsorption of colloidal gold. The entire structure revealed by the platinum impregnation allowed the anatomical assignment of the gold‐stained structures. Selective staining and specific visualization of biological tissues at micrometer resolution should elucidate the three‐dimensional cellular organization essential for the understanding and application of biological microstructures.     

Surface morphology and in vitro release performance of double-walled PLLA/PLGA microspheres entrapping a highly water-soluble drug

Double-walled microspheres trapping gentamicin sulphate were prepared from poly(l-lactic acid) (PLLA) and poly(l-lactic-co-glycolic acid) (PLGA) as a delivery system for highly hydrophilic antibiotics. The surface and cross-section morphology of the microspheres were characterized by SEM and FTIR. The diameters of the microspheres were ranging from about 50 μm to 700 μm. A low initial burst was achieved. The encapsulation efficiency was more than 70% and the cumulative drug release was about 40% for 30 days. The results indicated that the double-walled microspheres were able to achieve higher encapsulation efficiency and lower initial burst for highly water-soluble drugs.     

Encapsulation of SnO2/Sn Nanoparticles into Mesoporous Carbon Nanowires and its Excellent Lithium Storage Properties

A peculiar nanostructure of encapsulation of SnO₂/Sn nanoparticles into mesoporous carbon nanowires (CNWs) has been successfully fabricated by a facile strategy and confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high‐resolution TEM (HRTEM), X‐ray diffraction (XRD), BET, energy‐dispersive X‐ray (EDX) spectrometer, and X‐ray photoelectron spectroscopy (XPS) characterizations. The 1D mesoporous CNWs effectively accommodate the strain of volume change, prevent the aggregation and pulverization of nanostructured SnO₂/Sn, and facilitate electron and ion transport throughout the electrode. Moreover, the void space surrounding SnO₂/Sn nanoparticles also provides buffer spaces for the volumetric change of SnO₂/Sn during cycling, thus resulting in excellent cycling performance as potential anode materials for lithium‐ion batteries. Even after 499 cycles, a reversible capacity of 949.4 mAh g^?1 is retained at 800 mA g^?1. Its unique architecture should be responsible for the superior electrochemical performance.     

掺杂4-苯基卟啉的聚苯乙烯／二氧化硅复合纳米微球的制备

采用溶胶-凝胶法,首先利用苯乙烯与3-甲基丙烯酰氧基丙基三甲氧基硅烷(KH-570)化学反应合成共聚前驱物,利用TEOS在一定的条件下水解与缩合,一步合成了有机-无机复合纳米微球。用扫描电镜、红外光谱对共聚物及复合纳米粒子进行了表征。将非水溶性发光材料四苯基卟啉掺杂其中,制备出荧光复合纳米粒子。该粒子表现出了良好的发光性能,染料泄漏与猝灭几乎为零,可以作为一种新型的高效率的生物标记材料。     

Trapping and release of citrate-capped gold nanoparticles

An electrical method to trap and release charged gold nanoparticles onto and from the surface of gold electrodes modified by an alkanethiol self-assembled monolayer (SAM) is presented. To form electrodes coated with gold nanoparticles (GNPs), amine-terminated SAMs on gold electrodes were immersed in a solution of negatively charged citrate-capped GNPs. Accumulation of GNPs on the electrode surface was monitored by a decrease in the impedance of the SAM-modified electrode and by an increase in the electrochemical activity at the electrode as shown through cyclic voltammetry (CV). Electrostatic interactions between the GNPs and the amine-terminated SAM trap the GNPs on the electrode surface. Application of a subsequent negative bias to the electrode initiated a partial release of the GNPs from the electrode surface. Impedance spectroscopy, cyclic voltammetry, ultraviolet-visible (UV-Vis) spectroscopy and atomic force microscopy (AFM) were used to monitor and confirm the attraction of GNPs to and release from the aminealkanethiolated gold electrodes. This work describes a method of trapping and release for citrate-capped GNPs that could be used for on-demand nanoparticle delivery applications such as in assessing and modeling nanoparticle toxicology, as well as for monitoring the functionalization of gold nanoparticles.     

异烟肼乳酸-乙醇酸共聚物磁性微球的制备和体外释放

采用化学共沉法制备磁性Fe3O4纳米粒,再采用W/O/W复乳-溶剂挥干法制备异烟肼乳酸-乙醇酸共聚物[Poly(lactide-co-glycolide),PLGA]磁性微球(INH-PLGA-MMS);电镜考察INH-PLGA-MMS形态、激光粒径分析仪考察粒径分布、磁场计测定磁感应强度、高效液相色谱法(HPLC)测定包封率、载药量及其释放度。结果表明,W/O/W复乳-溶剂挥干法制得的INH-PLGA-MMS外观圆整、表面光滑,平均粒径为3.02μm,磁感应强度为11.403emu/g,平均包封率为62.52%,平均载药量为9.21%,体外释放表明该制剂具有明显的缓释功能,外加振荡磁场可以增加磁性微球中药物的释放。     

Gelatin–Chitosan composite capped gold nanoparticles: a matrix for the growth of hydroxyapatite

Growth of hydroxyapatite (HA) on gelatin–chitosan composite capped gold nanoparticles is presented for the first time by employing wet precipitation methods and we obtained good yields of HA. Fourier transform infrared spectroscopy (FTIR) spectrum has shown the characteristic bands of phosphate groups in the HA. Scanning electron microscopy (SEM) pictures have shown spherical nanoparticles with the size in the range of 70–250 nm, whereas ≥2–50 nm sized particles were visualized in high resolution transmission electron microscopy (HR-TEM). X-ray diffraction (XRD) spectrum has shown Bragg reflections which are comparable with the HA. Energy dispersive X-ray (EDX) studies have confirmed calcium/phosphate stoichiometric ratio of HA. The thermogravimetric analysis (TGA) has shown about 74% of inorganic crystals in the nanocomposite formed. These results have revealed that gelatin–chitosan capped gold nanoparticles, acted as a matrix for the growth of HA.