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Researchers reveal fate of nanoparticles inside cells
452 The researchers have found that varying the noble gas ambient used during the thermal annealing of the Fe catalyst particles on a SiO2 /Si support in the presence of H2 and water vapor appears to determine the flavor of the carbon nanotubes that are subsequently grown. Using He as the annealing ambient preferentially produces metallic nanotubes, while Ar favors semiconducting nanotubes. Detailed analysis using in situ transmission electron microscopy reveals that the carrier gas radically changes the shape and size of the Fe catalyst particles. In the presence of He, the particles form pronounced facets and exhibit a narrow size distribution. Conversely, with Ar the changes are reversed and the particles become more rounded and larger (Fig. 1). ‘‘[This] is the first demonstration of a deterministic relationship between the catalyst state and the resulting nanotube structure,’’ says Stach. ‘‘Our results indicate that you might be able to control the size and shape of the catalyst sufficiently to control the structure and thus the conductivity of the nanotubes.’’
C. Sealy What the researchers do not know, admits Stach, but are now working on, is whether it is the narrowly defined particle size that determines the formation of metallic nanotubes or the faceting that controls chirality. Harutyunyan believes the presence of trace amounts of water vapor is crucial to the formation of facets in the presence of He through a process of absorption-induced reconstruction. The findings could be a breakthrough in the controlled growth of nanotubes, say experts, if the results can be reproduced. ‘‘The achieved level of metallic composition is impressive,’’ says Boris I. Yakobson of Rice University. ‘‘If confirmed and scaled up, this is bound to make a major impact on a variety of tantalizing technological applications discussed for a least a decade from nanoelectronics and sensors to specialty composites and large-scale power transmission lines.’’ E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.003
Researchers reveal fate of nanoparticles inside cells Cordelia Sealy Most nanoparticles for biological and medical applications are functionalized with surface peptides and proteins. But what happens to this layer inside cells is of crucial importance to their ability to target specific types or areas of cells and trigger a response. Researchers from the Universities of Liverpool and Bordeaux think that they may have found the answer [V. Seé et al., ACS Nano 3 (2009) 2461]. Using three types of microscopy, including transmission electron microscopy, the British and French researchers looked at the localization of nanoparticles in cells and the integrity of a surface protein layer. ‘‘We’ve known for some time that nanoparticles are taken into cells and there have been experiments done to establish their final destinations, but we didn’t know until now what state they are in by the time they get there,’’ says Raphaël Lévy from the University of Liverpool. The researchers have found that when nanoparticles encounter a region of the cell called the endosome after being engulfed, the surface peptide/protein layer is degraded by a protease called cathepsin L. The degradation of the surface layer is likely to result in the loss of functionality of the nanoparticle, reducing or even eliminating its activity (Fig. 1). ‘‘The results are highly significant because cathepsin L has a very low specificity,’’ explains Lévy. ‘‘The degradation is likely to affect most bioconjugated nanoparticles.’’ While previous studies have looked at how the size and shape of nanoparticles affects entry into cells, the role of surface chemistry has been more difficult to unravel.
Figure 1 (Top) Transmission electron micrograph of nanoparticles trapped in an endosome. (Bottom) Overlay of bright field image of Hela cells and photothermal image showing nanoparticle localization. (Right) Three-dimensional rendering of the protease cathepsin L (produced with PyMOL, http://www.pymol.org). (Credit: Umbreen Shaheen for TEM image and Yann Cesbron for photothermal image.)
News and opinions ‘‘This degradation is an important issue since most nanomaterials enter the cell via endocytosis,’’ says Vince Rotello of the University of Massachusetts at Amherst. ‘‘Those of us looking to control intracellular localization of nanoparticles will have to go back to the drawing board.’’ The results indicate that designing intracellular nanoparticles or devices must take into account cathepsin L degradation of surface layers by inhibiting its activity or find a way to bypass the endosome when entering a cell.
453 Lévy believes it could be very challenging to develop nanoparticles able to avoid or rapidly escape the endosome. The alternative route of developing systems that resist cathepsin L degradation is more promising. ‘‘For peptides, this can be achieved using enantiomers or other synthetic analogs that are resistant to protease degradation,’’ he told Nano Today. E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.002
Polymer nanotubes improve connection to brain implants Cordelia Sealy Coating brain implants with conducting polymer nanotubes improves device performance and could potentially increase device longevity, according to new findings from researchers at the University of Michigan [M.R. Abidian et al., Adv. Mater. 21 (2009) 3764]. In the desire to find treatments for neurodegenerative diseases like Parkinson’s or repair function after trauma, efforts have focused on developing implanted neutral electrodes that record and deliver signals from brain tissue. Such implants, which are typically made to/from metals like Au or Pt, have to work for anything from a few hours to years on end. There is a trade-off between the size of these devices and the quality of the signal. Reducing the size of electrodes lessens their invasiveness but increases their impedance, to the detriment of the signal quality. Nanostructured materials offer a promising route to meet the conflicting requirements of smaller size, desirable electronic characteristics and biocompatibility. The University of Michigan researchers have found that coating the microelectrode recording sites of neural implants with poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes decreases the device impedance and improves sensitivity. The seven-week test of implants in six rats revealed high-quality unit activity (where the signal-tonoise ratio is over 4) in 30% more of the coated devices than uncoated. But the researchers believe that using polymer nanotubes could have additional advantages. Their unique structure could be used to deliver anti-inflammatory or other agents to reduce immune response and local scarring, supporting the longer term use of implants (Fig. 1). ‘‘This study paves the way for smart recording electrodes that can deliver drugs to alleviate the immune response of encapsulation,’’ says Mohammad Reza Abidian. He also adds that the PEDOT nanotubes could be used as a novel method for biosensing to indicate the transition between acute and chronic responses in the brain. PEDOT has already been demonstrated to be biocompatible, while the nanotubes themselves have both high conductivity and good chemical stability.
Figure 1 Illustration of firing neutrons (green structures) communicating with polymer nanotubes. (Credit: Mohammad Reza Abidian.)
‘‘This approach is powerful in that the PEDOT nanotubes help to decrease initial impedance, which is critical for device performance, while having the flexibility to deliver drugs to help control the inflammatory and tissue responses, which will ultimately be necessary for long-term performance of neural electrodes,’’ says Christine E. Schmidt of the University of Texas at Austin. E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.004
C. Sealy What the researchers do not know, admits Stach, but are now working on, is whether it is the narrowly defined particle size that determines the formation of metallic nanotubes or the faceting that controls chirality. Harutyunyan believes the presence of trace amounts of water vapor is crucial to the formation of facets in the presence of He through a process of absorption-induced reconstruction. The findings could be a breakthrough in the controlled growth of nanotubes, say experts, if the results can be reproduced. ‘‘The achieved level of metallic composition is impressive,’’ says Boris I. Yakobson of Rice University. ‘‘If confirmed and scaled up, this is bound to make a major impact on a variety of tantalizing technological applications discussed for a least a decade from nanoelectronics and sensors to specialty composites and large-scale power transmission lines.’’ E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.003
Researchers reveal fate of nanoparticles inside cells Cordelia Sealy Most nanoparticles for biological and medical applications are functionalized with surface peptides and proteins. But what happens to this layer inside cells is of crucial importance to their ability to target specific types or areas of cells and trigger a response. Researchers from the Universities of Liverpool and Bordeaux think that they may have found the answer [V. Seé et al., ACS Nano 3 (2009) 2461]. Using three types of microscopy, including transmission electron microscopy, the British and French researchers looked at the localization of nanoparticles in cells and the integrity of a surface protein layer. ‘‘We’ve known for some time that nanoparticles are taken into cells and there have been experiments done to establish their final destinations, but we didn’t know until now what state they are in by the time they get there,’’ says Raphaël Lévy from the University of Liverpool. The researchers have found that when nanoparticles encounter a region of the cell called the endosome after being engulfed, the surface peptide/protein layer is degraded by a protease called cathepsin L. The degradation of the surface layer is likely to result in the loss of functionality of the nanoparticle, reducing or even eliminating its activity (Fig. 1). ‘‘The results are highly significant because cathepsin L has a very low specificity,’’ explains Lévy. ‘‘The degradation is likely to affect most bioconjugated nanoparticles.’’ While previous studies have looked at how the size and shape of nanoparticles affects entry into cells, the role of surface chemistry has been more difficult to unravel.
Figure 1 (Top) Transmission electron micrograph of nanoparticles trapped in an endosome. (Bottom) Overlay of bright field image of Hela cells and photothermal image showing nanoparticle localization. (Right) Three-dimensional rendering of the protease cathepsin L (produced with PyMOL, http://www.pymol.org). (Credit: Umbreen Shaheen for TEM image and Yann Cesbron for photothermal image.)
News and opinions ‘‘This degradation is an important issue since most nanomaterials enter the cell via endocytosis,’’ says Vince Rotello of the University of Massachusetts at Amherst. ‘‘Those of us looking to control intracellular localization of nanoparticles will have to go back to the drawing board.’’ The results indicate that designing intracellular nanoparticles or devices must take into account cathepsin L degradation of surface layers by inhibiting its activity or find a way to bypass the endosome when entering a cell.
453 Lévy believes it could be very challenging to develop nanoparticles able to avoid or rapidly escape the endosome. The alternative route of developing systems that resist cathepsin L degradation is more promising. ‘‘For peptides, this can be achieved using enantiomers or other synthetic analogs that are resistant to protease degradation,’’ he told Nano Today. E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.002
Polymer nanotubes improve connection to brain implants Cordelia Sealy Coating brain implants with conducting polymer nanotubes improves device performance and could potentially increase device longevity, according to new findings from researchers at the University of Michigan [M.R. Abidian et al., Adv. Mater. 21 (2009) 3764]. In the desire to find treatments for neurodegenerative diseases like Parkinson’s or repair function after trauma, efforts have focused on developing implanted neutral electrodes that record and deliver signals from brain tissue. Such implants, which are typically made to/from metals like Au or Pt, have to work for anything from a few hours to years on end. There is a trade-off between the size of these devices and the quality of the signal. Reducing the size of electrodes lessens their invasiveness but increases their impedance, to the detriment of the signal quality. Nanostructured materials offer a promising route to meet the conflicting requirements of smaller size, desirable electronic characteristics and biocompatibility. The University of Michigan researchers have found that coating the microelectrode recording sites of neural implants with poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes decreases the device impedance and improves sensitivity. The seven-week test of implants in six rats revealed high-quality unit activity (where the signal-tonoise ratio is over 4) in 30% more of the coated devices than uncoated. But the researchers believe that using polymer nanotubes could have additional advantages. Their unique structure could be used to deliver anti-inflammatory or other agents to reduce immune response and local scarring, supporting the longer term use of implants (Fig. 1). ‘‘This study paves the way for smart recording electrodes that can deliver drugs to alleviate the immune response of encapsulation,’’ says Mohammad Reza Abidian. He also adds that the PEDOT nanotubes could be used as a novel method for biosensing to indicate the transition between acute and chronic responses in the brain. PEDOT has already been demonstrated to be biocompatible, while the nanotubes themselves have both high conductivity and good chemical stability.
Figure 1 Illustration of firing neutrons (green structures) communicating with polymer nanotubes. (Credit: Mohammad Reza Abidian.)
‘‘This approach is powerful in that the PEDOT nanotubes help to decrease initial impedance, which is critical for device performance, while having the flexibility to deliver drugs to help control the inflammatory and tissue responses, which will ultimately be necessary for long-term performance of neural electrodes,’’ says Christine E. Schmidt of the University of Texas at Austin. E-mail address: [email protected] 1748-0132/$ — see front matter doi: 10.1016/j.nantod.2009.10.004