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  • 8/12/2019 NANOPARTIKEL FOR BRAIN.pdf

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    MAY 2006 | VOLUME 1 | NUMBER 2

    RESEARCH NEW

    Using nanoparticles (NPs) for drug delivery of

    anticancer agents has significant advantagessuch as the ability to target specific locations in

    the body, the reduction of the overall quantity

    of drug used, and the potential to reduce the

    concentration of the drug at nontarget sites

    resulting in fewer unpleasant side effects.

    For intravenously injected particles,

    biocompatibility is the first issue. The second is

    to promote specific carrier-target interactions

    or devise specific carrier physicochemical

    properties to enable selective targeting. Recent

    research has made advances on both fronts.

    Researchers from Harvard Medical School,

    Massachusetts Institute of Technology (MIT),

    MIT-Harvard Center for Cancer NanotechnologyExcellence, and Gwangju Institute of Science

    and Technology in Korea have reported the

    successful use of targeted NP-aptamer

    bioconjugates for in vivochemotherapy

    [Farokhzad et al., Proc. Natl. Acad. Sci. USA

    (2006) 103, 6315]. The aim of the joint effort of

    Omid C. Farokhzad and Robert Langers groups

    was to design a system able to target cancer

    cells specifically, introduce chemotherapy drugs

    directly into the cells and release them over

    time, and avoid uptake by noncancerous cells.

    To achieve this, the researchers devised a NP-based system using biodegradable and

    biocompatible poly(D,L-lactic-co-glycolic acid).

    An anticancer drug, in this case docetaxel (Dtxl),

    is encapsulated in the 150 nm NPs. The surface

    of the NPs is then functionalized with aptamers

    (Apt) nucleic acid ligands that promote cell-

    specific uptake by binding to target antigens,

    analogous to antibodies. In this case, the RNA

    aptamers that recognize the prostate-specific

    membrane antigen (PSMA), which is expressed

    by prostate cancer cells, are used. The NPs are

    also functionalized with poly(ethylene glycol)

    (PEG) to reduce uptake by tissue macrophagesand nontargeted cells. The polymeric NPs

    dissolve slowly once inside the cancerous cell,

    releasing the Dtxl. The rate of dissolution can be

    designed into the system so that drugs are

    released over a predetermined time.

    After a single administration of the Dtxl-NP-Apt

    bioconjugates into mice, which had been

    implanted with human prostate cancer cell

    lines, five out of seven animals showed

    complete tumor reduction and all survived the

    109-day study. The ability to treat tumors in

    one go is particularly attractive. Early diagnosis

    of cancer creates the opportunity for localized

    treatment options, explains Farokhzad.Since all of the components of the NP-based

    system, except the RNA aptamers, are already

    approved by the Food and Drug Administration

    for clinical use, Farokhzad is confident that such

    NP-based treatment systems could be feasible

    in the near future, not only for cancer but other

    diseases as well. As Langer explains, [we] can

    put different things inside or on the outside of

    the NPs. This technology can be applied to

    almost any disease.

    Cordelia Sealy

    Nanoparticles target cancer cells in vivoNANOPARTICLES

    Nanoparticles turn up the heatNANOPARTICLES

    Researchers from Ohio University have developed a

    novel way of studying the heat generated by metal

    nanoparticles (NPs), especially Au, under optical

    illumination. [Richardson et al., Nano Lett. (2006) 6,

    783].

    We wanted to understand how much heat can be

    generated locally by nanoscale metal NPs when

    illuminated with light, explains Alexander O. Govorov.

    By using an ice matrix and observing the melting

    effect, Hugh H. Richardson and coworkers were able to

    characterize the heat generated by Au NPs.This heat can be so intense that the melting of the

    ice matrix looks like a nano-explosion, says Govorov.

    The researchers found a strong dependence of the

    melting effect on position, which they believe is the

    result of the NPs with different geometries forming

    complexes. Since each geometry has a unique thermal

    response, this leads to an overall mesoscopic character

    for the heat generation. The heat generation is also

    enhanced in a collection of NPs.

    The heat generation capabilities of NPs have been

    suggested for several applications, including protein

    labeling for all-optical imaging, fabricating composites

    with novel thermal and optical properties, remote

    release of drugs when excited by light, and

    photothermal therapy for cancer treatment. This last

    application has been the focus of much research in the

    medical field. Recently, researchers from Georgia

    Institute of Technology and the University of

    California at San Francisco have found that Au

    nanoparticles can be made to absorb and scatter much

    more strongly in the near-infrared region if they are

    rod-shaped [Huang et al.,J. Am. Chem. Soc. (2006)

    128, 2115]. The Au nanorods are synthesized and

    conjugated to anti-epidermal growth factor receptor

    monoclonal antibodies so that they bind onto thesurface of malignant cancer cells. The bound nanorods

    make the malignant cells clearly visible when observed

    in dark field, using a laboratory microscope. The

    malignant cells also require only about half the laser

    energy required to destroy nonmalignant cells

    photothermally. The use of Au nanorods allows both

    effective cancer cell diagnosis and photothermal

    therapy, say the researchers.

    Cordelia Sealy

    A model of Au NPs excited with laser light andresults of calculated temperature increase for acomplex of 16 NPs (left). A surface map of the iceusing Raman spectroscopy. A crater on the surfaceof the ice after massive heat generation from AuNPs is visible (right). (Courtesy of Alexander O.Govorov.)

    Prostate cancer cells that have taken upfluorescently labeled NPs (red) and can releasechemotherapy drugs. The cells nuclei andcytoskeletons are stained blue and green.(Courtesy of Benjamin A. Teply.)

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    MAY 2006 | VOLUME 1 | NUMBER 20

    RESEARCH NEWS

    Itamar Willner and colleagues at the Hebrew

    University of Jersusalem, Israel have devised an

    alternative to the polymerase chain reaction (PCR) for

    the amplified detection of DNA [Weizmann et al.,

    Angew. Chem. Int. Ed. (2006) 45, 2238].

    PCR is the standard method for amplifying nucleic

    acids for analysis, diagnosis, and manipulation. It is thekey that has advanced genome research, genetic

    engineering, and DNA analysis. However, the PCR

    process suffers from basic limitations, as it is error

    prone, requires long analysis time intervals, and the

    quantification of the analyzed DNA is limited,

    explains Willner.

    This led the researchers to design and demonstrate

    another method based on a DNA/enzyme machine

    that, on detection of a specific target sequence, is

    activated to devour a supply of DNA fuel, giving a

    fluorescent waste product and a further machine. The

    formation of more DNA-cutting machines accelerates

    further cleavage of the fuel, amplifying the fluorescent

    signal that is produced, so it is large enough to be

    detected.

    The researchers demonstrate the potential of theirsystem by detecting one of the genetic mutations

    characteristic of Tay-Sachs disease. The disease is fatal

    in early childhood and the defective gene is thought to

    be carried by 1 in 30 Ashkenazi Jews. The system was

    able to detect the mutation with a sensitivity limit of

    10 fM. The normal sequence gives a much smaller

    signal even at micromolar levels, and other DNA

    sequences give no detectable signal at all.

    Despite this ultrahigh sensitivity, the researchers note

    a saturation in fluorescent signal. Changes of orders of

    magnitude in the concentration of the mutated

    sequence are observed as only relatively small changes

    in the evolved fluorescence.

    The practical applications of such systems are

    enormous, says Willner. DNA machines may be used

    for the rapid analysis of pathogens or geneticdisorders. We believe that the development... is a

    general, new scientific paradigm.

    The group is already developing simpler and more

    effective machines. Furthermore, the method is not

    limited to DNA sensing. The machines can be

    conjugated to protein antigen/antibody complexes to

    provide a whole new sensing area for bioanalytics,

    Willner told Nano Today.

    Jonathan Wood

    Biomolecular machine provides alternative to PCRNANOBIOTECHNOLOGY

    Technique images proteins in living cell membranesCHARACTERIZATION

    A scanning probe microscopy technique has been

    adapted by a group of UK and US researchers to

    allow the imaging of individual protein complexeson the surfaces of live cells [Shevchuk et al.,

    Angew. Chem. Int. Ed. (2006) 45, 2212]. The

    advance should open up new areas of membrane

    biology, say the researchers from the University

    of Cambridge, Imperial College London, The

    Babraham Institute, Ionscope, and the University

    of Kentucky.

    There has been a great deal effort to use

    scanning probe microscopies to image proteins

    and structures on live cells directly, but without

    much success since the cell surface is both soft

    and responsive, explains David Klenerman of the

    University of Cambridge.

    The team adapted a technique called scanning ionconductance microscopy (SICM) developed by

    Paul Hansma and colleagues, improving the

    resolution by an order of magnitude.

    We believe [this] to be a major breakthrough,

    says Klenerman. While such experiments have

    been proposed ever since scanning probe

    microscopy was developed 25 years ago, this is

    the first time that they have been achieved. This

    is not an iterative improvement in resolution but

    a quantum step, since it allows individual protein

    complexes to be imaged directly on the

    membrane of live cells and their dynamics to be

    followed.

    A nanoscale pipette is used as the scanning probein SICM, and the ion current between an

    electrode in the pipette and an electrode in the

    sample chamber is used as the feedback control.

    The probe senses a reduction in ion current when

    a surface is encountered within a hemisphereextending from the pipette tip with the same

    radius as the pipettes inner radius. This means

    that sensing is both vertical and lateral under the

    tip, helping to prevent the pipette walls from

    touching the cell surface.

    Quartz pipettes with an inner diameter of 13 nm

    were used in a SICM system with enhanced

    mechanical stability and custom-designed

    software. The resolution of the instrument was

    tested by imaging a monolayer of bacterial

    proteins arranged in a square lattice with a

    spacing of 13.1 nm. The individual protein

    molecules are clearly identifiable, and a fast

    Fourier transform of the image indicates that thelateral resolution is ~3-6 nm.

    Having determined the capabilities of their SICM

    setup, the group imaged the plasma membranes

    of sperm cells. Under certain conditions, these

    cells exhibit protrusions that are generallythought to be transmembrane proteins or protein

    complexes. SICM could visualize these

    protrusions, showing two populations with

    diameters of ~14 nm and ~30 nm in size. The

    researchers observations reveal that a small

    number of these proteins diffuse, disappear, or

    appear over time in the cell surface, showing the

    SICM technique can also follow changes in

    membrane structure.

    The next steps are to continue to improve the

    instrument both hardware and software and

    exploit the new capabilities to follow biological

    processes on live cells down to the level of single

    molecules, says Klenerman.Jonathan Wood

    SICM images of protein complexes in the surface of a sperm cell membrane. The images in (a) are taken10 min apart. Areas where the position and shape of the proteins change over time are circled. By coloringthe two images red and green, then overlapping them (b), the changes are immediately apparent.( 2006 Wiley-VCH.)

    (a) (b)

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    MAY 2006 | VOLUME 1 | NUMBER 2

    RESEARCH NEW

    Researchers from the University of

    Chicago and Argonne National

    Laboratory believe that they have

    revealed the mechanism for the self

    assembly of large areas of nanocrystal

    monolayers [Bigioni et al., Nat. Mater.

    (2006) 5, 265].

    A lacy coffee-stain-like ring of material

    with clumps of particles is usually left

    behind when a drop of a colloidal

    solution of nanoparticles (NPs) dries

    on a surface. However, an alternative

    drying behavior that produces highly

    uniform, long-range-orderednanocrystal monolayers is possible. In

    this regime, the morphology of a NP

    film is controlled by evaporation

    kinetics and particle interactions with

    the liquid-air interface. At the start of

    the process, a saturated two-

    dimensional solution of NPs forms at

    the liquid-air interface. Monolayer

    islands of nanocrystals form on the top

    surface of the drop, which grow and

    merge to form a continuous

    monolayer over the entire liquid-air

    interface. Unlike ordinary two-dimensional growth, the islands show

    exponential and linear growth

    behaviors. This creates monolayers

    with exceptional long-range order and

    an extraordinary degree of perfection

    (of up to 108 particles), say the

    researchers. The monolayer shows no

    lace- or ring-like patterns and no

    clumps of particles. The researchers

    suggest two requirements for such

    highly ordered self-assembly: (1) rapid

    evaporation (to segregate particles

    near the liquid-air interface); and

    (2) an attractive interaction between

    the particles and liquid-air interface

    (to localize them on the interface).

    This drop-dry self-assembly method is

    simple, robust, scalable, and insensitive

    to substrate material or topography,

    making it an excellent candidate for

    the fabrication of ultrathin films.

    Cordelia Sealy

    Self-assembly

    leaves no stainNANOPARTICLES

    Blood compatibility is a vital

    property for biomedical devices

    intended for use in vivo.

    Researchers from Rensselaer

    Polytechnic Institute (RPI) and

    Albany College of Pharmacy

    have developed blood-

    compatible carbon nanotubes

    that could form the basis of

    new generations of nanodevicesfor medical applications

    [Murugesan et al., Langmuir

    (2006) 22, 3461].

    The design of blood-compatible devices primarily relies on

    the immobilization of the glycosaminoglycan (GAG) heparin

    on their surfaces. Proteoglycans (PGs), consisting of a core

    protein to which multiple GAG chains are linked, have

    essential physiological, biochemical, and structural functions

    within the body. Consequently, the researchers combined

    these structures with carbon

    nanotubes. We applied some

    activation-coupling chemistry,

    which we had previously

    developed for the preparation of

    blood-compatible plastics, to

    carbon nanotubes, explains

    Robert J. Linhardt of RPI. The

    researchers replaced the core

    protein of PGs with multiwalledcarbon nanotubes (MWNTs) and

    heparinized the material in a

    three-stage process.

    We believe this represents a new enabling technology in the

    field of nanomedicine, says Linhardt. It could be useful for

    artificial or reconstruction of blood vessels, blood-compatible

    dialyzers, and drug delivery systems. The researchers are now

    undertaking in vivoanimal studies.

    Cordelia Sealy

    Designing in blood compatibilityCARBON NANOTUBES

    Nanorice combines best of both worlds

    NANOPARTICLES

    The plasmonic properties of metallic

    nanostructures, where light interacts

    with free electrons giving rise to

    collective oscillations of charge density,

    are attracting interest for a range of

    applications. However, the rational

    design and control of nanostructures

    with structurally tunable plasmon

    resonances and large, well-defined

    optical fields is needed for real devices.

    There are two current approaches,

    both of which produce structures with

    two tunable plasmon resonances:

    cylindrical nanoparticles, or nanorods,

    and dielectric core-metal shell

    nanoparticles, or nanoshells.Researchers from Rice University

    have devised a hybrid nanoparticle

    geometry that combines the plasmonic

    properties of both nanorods and

    nanoshells [Wang et al., Nano Lett.

    (2006) 6, 827].

    The rice-shaped nanoparticle consists

    of a hematite dielectric core with a

    nanometer-thick Au shell. We [grew] a

    thin, homogeneous Au shell around a hematite particle

    to create a layered nanostructure with a shape known

    as a prolate spheroid, explains Naomi J. Halas. The

    strong resemblance of the resulting

    particles to grains of rice earned them

    their moniker. Nanorice are special

    particles because they truly are

    hybrids, combining the tunable

    plasmon properties of nanoshells with

    the high field focusing shape of

    nanorods in a single particle, says

    Halas. The results indicate that

    plasmon tunability arising from

    variation in the shell thickness is far

    more geometrically sensitive than

    that arising from variation of the

    length of the nanorice. Furthermore,

    the plasmon modes of nanorice can be

    tuned across a broader spectral rangethan either nanorods or nanoshells.

    The strong, tunable local fields make

    nanorice suitable for surface-

    enhanced spectroscopy sensing

    substrates. The optical properties of

    these nanoparticles are ideal for

    sensing applications, says Halas.

    Nanorice has advantages for

    spectroscopic sensing and

    characterization of large biomolecules, like proteins and

    DNA, or biological samples.

    Cordelia Sealy

    Schematic of Au-coated hematitenanostructure (top). Transmissionelectron micrograph of nanorice(middle). Calculated localelectromagnetic field for nanoriceilluminated at its plasmon resonantfrequency by light polarized in thelongitudinal axis of the structure(bottom). [Credit: Hui Wang andFei Lee, Rice University.]

    (Image courtesy of Robert J. Linhardt.)

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    MAY 2006 | VOLUME 1 | NUMBER 2

    RESEARCH NEW

    Both the size and shape of Au nanoparticles (NPs)

    affects their uptake by mammalian cells, according

    to research from the University of Toronto,

    Canada [Chithrani et al., Nano Lett. (2006) 6,

    662]. The findings could influence the design of

    more complex NPs being developed for biomedical

    applications.

    Fine-tuning the properties of NPs generally

    involves altering their size and shape. However,

    little is known about how such structural

    reengineering can alter the nanostructures

    interactions with cells. But measures that promote or

    impede cellular uptake could have importantimplications for the efficacy of biomedical applications.

    This information could also help inform toxicity

    studies.

    Previously, researchers just looked at targeting

    molecules on the surface of the nanostructures to

    dictate uptake, says Warren C. W. Chan. It was

    speculated that size and shape may influence how

    nanostructures go into cells. However, no one

    conducted a full study.

    Chan and colleagues performed their investigations on

    spherical and rod-shaped colloidal Au NPs 14-100 nm

    in diameter. The nanostructures were incubated for6 hours with HeLa cells in solution containing growth

    medium and 10% serum. Cellular uptake of the NPs

    can be observed using transmission electron

    microscopy (TEM). Concentrations of Au within the

    cells were measured using inductively coupled plasma

    atomic emission spectroscopy.

    A comparison of differently sized nanostructures

    reveals that the HeLa cells accept more 50 nm

    particles than any other. The greatest number of

    50 nm NPs entering a cell was over 6000, whereas

    maximum uptake for 14 nm and

    74 nm sized NPs was only around 3000. The team

    also observed significant variations in uptake

    concentration for differently-shaped particles. For

    instance, HeLa cells ingested 500% more 74 nm

    spherical NPs and 375% more 14 nm spherical

    NPs compared with the same size rod-shaped

    particles.

    Chan acknowledges that alternative nanostructure-

    cell combinations could yield quite different results.

    Uptake mechanisms could hinge on the number of

    receptors that certain cells have and how thosereceptors are clustered. The nature of molecules bound

    to different NPs could also influence uptake processes.

    All these variables need to be investigated.

    This is the first study, Chan told Nano Today. We

    really have to develop a full understanding of the

    interface between nanostructures and biological

    systems to develop knowledge of how to design these

    nanostructures for biology.

    Paula Gould

    Size matters to cell uptake but so does shapeNANOPARTICLES

    Nanofiber scaffold repairs brain tissue

    BIOMATERIALS

    Researchers from Massachusetts Institute of

    Technology, University of Hong Kong, and the

    Fourth Military Medical University, Xian, China,have used a self-assembling peptide scaffold to

    repair severed brain structures in blind rodents

    and restore their sight [Ellis-Behnke et al., Proc.

    Natl. Acad. Sci. USA (2006) 103, 5054].

    The findings indicate that similar scaffolds could

    be used to restore some critical functionality in

    human victims of traumatic brain injury.

    Restoring functionality, such as speech or sight,

    following damage to the central nervous system

    involves promoting the regrowth of branch-like

    axons. Broken neuronal connections, which carry

    out vital communications, can then be reinstated.

    However, this is typically hampered by the

    formation of scar tissue, the emergence of gaps in

    nervous tissue, and the failure of many adult

    neurons to initiate axonal extension.

    The researchers opted to use a highly hydrated

    nanofiber scaffold, formed spontaneously from

    peptides, to create an environment conducive to

    axon regeneration. They severed the optic nerve

    of immature and adult hamsters, then injected

    1% peptide scaffold solution directly into the

    injury site. Subsequent follow-up revealed that

    the gaps in the brain tissue had closed up and

    axons had regrown across the lesion sites.

    Behavioral studies on the treated adult rodents

    indicated that six out of eight could respond to

    visual cues. The two nonresponders had suffered

    vascular injury during surgery. The treated groups

    vision improved as testing progressed, indicating

    the value of long-term rehabilitation.

    The peptide scaffold has several advantages that

    make it particularly suited to brain repair,

    according to Rutledge G. Ellis-Behnke. The self-

    assembling material can fill the voids of anirregular cut, brain cells migrate into the scaffold,

    it is biodegradable (disappearing from the brain

    within about four weeks), and does not appear to

    provoke a significant immune response.

    While the material has considerable clinical

    potential, research is needed to optimize the

    scaffold formulation and understand how it might

    be administered to patients with severe traumatic

    brain injuries, says Ellis-Behnke. The team is taking

    a two-pronged approach. A study of chronic injury

    will assess the scaffolds performance in healing

    optic nerves that have been severed and left for

    up to a month. A second series of experiments will

    look more specifically at stroke.

    If we can reconnect parts of the brain that were

    disconnected by a stroke, then we may be able to

    restore speech to an individual who is able to

    understand what is said, but has lost the ability to

    speak, says Ellis-Behnke. This is not about

    restoring 100% of damaged brain cells, but 20%

    or even less may be enough to restore function,

    and that is our goal.

    Paula Gould

    Photo of a section from the brain of an 8-month-old hamster treated with a self-assembling peptidenanofiber scaffold at the time of surgery. Theaxons, shown by green fluorescence, have regrownthrough the cut and have formed functionalconnections at approximately 82% of normal

    density. (Courtesy of Rutledge G. Ellis-Behnke.)

    TEM images of Au nanoparticles with diameters of (a) 14 nm and(b) 50 nm in cells. (Courtesy of B. Devika Chithrani.)

    (a) (b)

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    MAY 2006 | VOLUME 1 | NUMBER 2

    RESEARCH NEW

    Researchers from the University of

    Zaragoza in Spain suggest that

    inorganic materials, such as silica, can

    offer the properties needed for

    nanoparticle (NP)-based drug delivery,

    namely nontoxicity, biocompatibility,

    high stability, and a hydrophilic and

    porous structure useful for tailoring

    the encapsulation of drugs [Arruebo

    et al., Chem. Mater. (2006), 18, 1911].

    We have developed silica particles

    belonging to the MCM family, as well

    as hollow silica microcapsules,

    explains Jesus Santamara. Fe is

    deposited inside the porous structure

    of the particles and microcapsules in

    order to obtain magnetic drug-delivery

    vectors. This enables the particles and

    capsules to be targeted to specific

    locations, such as a diseased organ, by

    a magnetic field.

    Both types of silica structure are small

    enough to be transported through the

    vascular system. The release rate from

    the silica structures could be

    controlled by adjusting their size and

    porous structure, suggests Santamara.The magnetic material is embedded

    inside the silica matrix, which has

    advantages in minimizing potential

    side effects.

    The researchers are undertaking in vivo

    animal studies and drug diffusion

    studies in simulated body fluids.

    Cordelia Sealy

    Silica key to

    drug deliveryNANOPARTICLES

    ZnO nanoparticles damage E. coli

    TOXICOLOGY

    Many concerns have been raised

    about the impact ofnanoengineered materials on

    the environment, so a study

    showing that ZnO nanoparticles

    can damage Escherichia colicells

    is likely to be the center of

    considerable scrutiny [Brayner

    et al., Nano Lett. (2006) 6, 866].

    The ZnO nanoparticles (NPs)

    used in the study are very similar to a semiconducting,

    crystalline form of TiO2 that is approved for use in

    sunscreens. TiO2 anatase has a band gap of 3.23 eV,

    while the gap for ZnO is 3.3 eV. Both materials can

    reflect and scatter ultraviolet (UV) A and B light. In

    addition, ZnO is of interest for a variety ofapplications in the microelectronics industry,

    including sensors, photocatalysis, solar cells,

    transparent electrodes, electroluminescent devices,

    and laser diodes.

    Researchers from the University of Paris 7 and the

    Museum of Natural History, Paris synthesized ZnO

    NPs in di(ethylene glycol) medium by forced hydrolysis

    of Zn2+ salts. Small molecules and macromolecules

    were added to control the size and shape of NPs. Their

    size, shape, and morphology were characterized by

    transmission electron microscopy (TEM) and X-ray

    diffraction. Then the team

    incubated E. coliovernight insolutions of ZnO NPs with

    differing concentrations

    (10-2 M to 10-4 M).

    Subsequent TEM analysis

    shows that lower

    concentrations of ZnO NPs

    induce no damage in E. coli

    cells. However, internalization

    of NPs within E. colicells and some cell leakage was

    observed at concentrations higher than 1.3 x 10-3 M.

    Internalization of ZnO NPs may be influenced by the

    attached molecules and macromolecules that were

    added to control size, says Roberta Brayner. The

    majority of NPs used by industry are stabilized bymolecules such as phosphines or surfactants such as

    sodium decylsulfate. These molecules can be toxic to

    living cells and the environment, she says. Very few

    studies have been done on the toxicological impact of

    these new hybrid nanomaterials.

    The researchers are also carrying out conductometric

    studies of cell content release, examining the effect of

    varying particulate size, shape, and concentration on

    bacterial growth, and looking at the mechanism of

    cellular internalization.

    Paula Gould

    E. coli cells seen before (a) and after (b) contactwith ZnO NPs. (Courtesy of Roberta Brayner.)

    (a) (b)

    The increased production of nanoparticles (NPs) is making it

    more likely that such materials will end up in watercourses,

    either as medical or industrial waste, or when used as

    ecological tools, with unknown consequences for aquatic life.

    Now, research has shown that both TiO2 and fullerene NPS

    can be harmful to the freshwater zooplankton Daphnia magna

    [Lovern and Klaper, Environ. Toxicol. Chem. (2006) 25, 1132].

    The researchers from the University of Wisconsin-Milwaukee

    used two alternative methods to prepare C60 and TiO2 NPs:

    filtration in tetrahydrofuran and sonication. The average

    diameter of the TiO2 particles is 10-20 nm, while that of C60is 0.72 nm. Groups of young D. magnawere then exposed to

    four test solutions with varying concentrations of NPs. The

    number of D. magnastill alive in each solution after 1 hour,

    24 hours, and 48 hours was assessed.

    Exposure to both filtered C60 and TiO2 caused mortality in the

    zooplankton. Filtered C60 proved to be lethal at much lower

    concentrations than TiO2, confirming suspicions that smaller

    particles could be more harmful. The method of NP

    preparation also appeared to affect toxicity. Solutions of

    unfiltered, sonicated TiO2 had little observable effect, even at

    high concentrations. Mortality rates for sonicated C60fluctuated considerably, rather than increasing steadily with

    concentration. The findings can be explained by the greater

    spread of particle size in unfiltered solutions and the tendency

    for particulate clumping, the researchers suggest.

    The results should be useful to those seeking to establish

    guidelines for nanoparticle handling and disposal, says Sarah B.

    Lovern. Daphniaare a great species to study because they

    have been used in toxicity tests for many other chemicals. So

    the results of this study can be compared to other studies ofpotentially harmful compounds, she says. The researchers are

    now focusing on other, nonlethal effects that fullerene and

    TiO2 NPs may have on aquatic organisms, as well as

    investigating other materials.

    Mortality is important, but Daphniachange their behavior

    when a contaminant is present in a body of water. These

    changes in behavior may make them more likely to be preyed

    upon by fish and could affect the food web, she says.

    Paula Gould

    Zooplankton suffer under nanoparticle exposureTOXICOLOGY

    Correction

    In the February issue of NanoToday, we mistakenly stated

    that the half-life of 18F is 11 min

    [Nano Today(2006) 1 (1), 13] ,

    as the result of a typographical

    error. The correct half-life is

    110 min. We thank Douglas

    Smyth of the Royal Adelaide

    Hospital in Australia for bringing

    this to our attention.