Drug delivery with nanoparticles

 Researchers are able to produce medicine encapsulated in nanoparticles the size of viruses, but new research has shown another great challenge in nanomedicine -- the immune system -- and the importance of the coating polymers on the nanoparticle surface.

Researchers have over time been able to show that medicine designed at nanoscale offers unprecedented opportunities for targeted treatment of serious diseases such as cancer. However, now research also shows that the body's immune system plays a significant part in the drug delivery process.

"Researchers today are able encapsulate medicine in nanoparticles the size of viruses. The nanoparticles are effective for drug delivery -- the delivery of the medicine to the body -- because they can very precisely find diseased cells and carry the medicine to them. This means that you can suffice with less dosage and thereby fewer side effects," explains Professor Moein Moghimi from the Faculty of Pharmaceutical Sciences at the University of Copenhagen.

Professor Moghimi has along with colleagues at the University of Brighton and the Technical University of Denmark recently published a landmark paper in ACS Nano regarding the immune system's attack on nanoparticles.

A water disguise

The new research has shown that the coating of the nanoparticle surface has great influence on the activation of the immune system -- the particle's polymer coating can be designed in various ways, and the form can drastically change the body's immune response.

"Drug delivery with nanoparticles camouflaged as water soluble polymers has proven very effective. One way of delivering drugs safely to diseased sites in the body is to encapsulate them in small polymeric particles in similar size to viruses. However, when injected into the blood these particles are intercepted by the body's defence system. This can be overcome by camouflaging the surface of these nanocarriers with water soluble polymers. This makes the surface 'water-like' and less visible to the immune system," says Professor Moghimi.

Significance of changing the coating polymers

Professor Moghimi works at the Department of Pharmaceutics and Analytical Chemistry where he heads the Centre for Pharmaceutical Nanotechnology and Nanotoxicology, which is supported by the Danish Agency for Science, Technology and Innovation. This work was done as part of ongoing research at the Centre.

Professor Moghimi's main focus is nanotoxicology -- and the possible consequences of drug delivery with nanoparticles.

"Our newest research indicates that we should be very cautious when designing the surface of the nanoparticles. Remarkably, changing the conformation of the coating polymers on nanoparticle surface from a 'mushroom-type' to a 'brush-type' appearance can switch complement activation from one pathway to another," explains Professor Moghimi.

The research demonstrates difficulty in design and surface engineering of polymeric nanoparticles such that it is hydrophilic enough to be compatible with biological fluids and yet prevent complement activation. This is also very important from clinical perspectives since complement activation may induce adverse reactions in some patients.

The importance of this work was also highlighted in an all exclusive "News and Views" by the journal Nature Nanotechnology.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Copenhagen.

Journal Reference:

Robert B. Sim, Russell Wallis. Surface properties: Immune attack on nanoparticles. Nature Nanotechnology, 2011; 6 (2): 80 DOI: 10.1038/nnano.2011.4

Drinking water: Nanomembranes could filter bacteria

 New nanomaterials research from the University at Buffalo could lead to new solutions for an age-old public health problem: how to separate bacteria from drinking water.

To the naked eye, both water molecules and germs are invisible -- objects so tiny they are measured by the nanometer, a unit of length about 100,000 times thinner than the width of a human hair.

But at the microscopic level, the two actually differ greatly in size. A single water molecule is less than a nanometer wide, while some of the most diminutive bacteria are a couple hundred.

Working with a special kind of polymer called a block copolymer, a UB research team has synthesized a new kind of nanomembrane containing pores about 55 nanometers in diameter -- large enough for water to slip through easily, but too small for bacteria.

The pore size is the largest anyone has achieved to date using block copolymers, which possess special properties that ensure pores will be evenly spaced, said Javid Rzayev, the UB chemist who led the study. The findings were published online on Jan. 31 in Nano Letters and will appear in the journal's print edition later this year, with UB chemistry graduate student Justin Bolton as lead author.

"These materials present new opportunities for use as filtration membranes," said Rzayev, an assistant professor of chemistry. "Commercial membranes have limitations as far as pore density or uniformity of the pore size. The membranes prepared from block copolymers have a very dense distribution of pores, and the pores are uniform."

"There's a lot of research in this area, but what our research team was able to accomplish is to expand the range of available pores to 50 nanometers in diameter, which was previously unattainable by block-copolymer-based methods," Rzayev continued. "Making pores bigger increases the flow of water, which will translate into cost and time savings. At the same time, 50 to 100 nm diameter pores are small enough not to allow any bacteria through. So, that is a sweet spot for this kind of application."

The new nanomembrane owes its special qualities to the polymers that scientists used to create it. Block copolymers are made up of two polymers that repel one another but are "stitched" together at one end to form the single copolymer.

When many block copolymers are mixed together, their mutual repulsion leads them to assemble in a regular, alternating pattern. The result of that process, called self-assembly, is a solid nanomembrane comprising two different kinds of polymers.

To create evenly spaced pores in the material, Rzayev and colleagues simply removed one of the polymers. The pores' relatively large size was due to the unique architecture of the original block copolymers, which were made from bottle-brush molecules that resemble round hair brushes, with molecular "bristles" protruding all the way around a molecular backbone.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University at Buffalo.

Journal Reference:

Justin Bolton, Travis S. Bailey, Javid Rzayev. Large Pore Size Nanoporous Materials from the Self-Assembly of Asymmetric Bottlebrush Block Copolymers. Nano Letters, 2011; : 110131160735014 DOI: 10.1021/nl103747m

A misunderstanding leads to method for making nanowells

A safe, simple, and cheap method of creating perfectly etched micron and smaller size wells in a variety of substrates has been developed by researchers in Penn State's Department of Chemical Engineering. Similar patterned surfaces are currently made using complex and expensive photolithography methods and etch processes under clean room conditions and used in the fabrication of many optical, electrical, and mechanical devices.

The nanowell discovery was made in the labs of Darrell Velegol and Seong Kim by Velegol's graduate student, Neetu Chaturvedi, and Kim's graduate student, Erik Hsiao. An article detailing their research, "Maskless Fabrication of Nanowells Using Chemically Reactive Colloids," appeared in the online edition of the journal Nano Letters in January 2011. In collaboration with Chaturvedi, Hsiao was working on a project to adhere polystyrene on a silicon wafer to create nanostructures with known dimensions. When Hsiao asked her to heat one of his samples, a miscommunication led her to heat the polystyrene and silicon wafer at low temperature in water in the autoclave normally used for biological samples rather than in the vacuum furnace. When they looked at the samples under the atomic force microscope (AFM), they noticed holes had formed beneath the polystyrene particles. Further examination under the scanning electron microscope (SEM) showed them perfectly etched, pyramidal shaped holes in the substrate below the places where the amidine-functionalized polystyrene latex colloid particles had adhered to the silicon dioxide on the surface of the silicon wafer.

"We saw three holes in the sample at the first AFM imaging and didn't know what it meant since we expected pancake-like polymer patches on the sample," said Hsiao. They took the sample to their advisers, who were both surprised by the etched wafer. By going over the steps the students had taken, the researchers realized that the wells were produced when the water hydrolized the amidine group in the particle, and through a series of chemical reactions, created a hydroxide ion that etched the well into the silicon wafer. The holes were uniform and their size and depth were totally dependent on the size of the original polystyrene particle, although the orientation of the silicon crystal affected the shape of the wells. In one orientation (100), the wells were perfect four-sided inverted pyramids. In the other orientation (111), the wells were perfect hexagons. The four researchers called them nanowells, because the bottom dimension of the wells was only a couple of nanometers across. They soon realized that they had discovered a new maskless method for creating structures in silicon without the elaborate steps normally required in the clean room.

"We're delivering hydroxide ions directly to where we want to etch," Velegol explained. "It's much safer and cheaper than electron beam and X-ray lithography. It's so safe that you could practically eat these particles without any harm."

"We think this is a quite general discovery," Kim added. "It's a way to deliver chemistry locally rather than in bulk. Many metals, ceramics, and other materials can be etched with this technique."

Another potential benefit of the discovery is the ability to create patterns on curved surfaces, something that is difficult to do with conventional photolithography. Since the particles are suspended in water, they can adhere to the surface of any shape and space themselves evenly over the surface. The researchers are just beginning to come up with intriguing ideas for how to use the simple technique.

Many breakthroughs come from accidents, Velegol remarked, because once something is known, people work on it very rapidly until they have filled in all the pieces and there is less to discover. Accidents are out of the pattern. "It's one of those situations like Pasteur said where chance favors the prepared mind. We would never even have thought to try this kind of chemistry. But Neetu had been working with these colloids for several years, and Erik had experience with the AFM, so they were well prepared to take advantage of the accident," Velegol concluded.

This work was supported by the National Science Foundation (Grant Nos. IDR-1014673 and CMMI-1000021).

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Penn State Materials Research Institute, via Newswise.

Journal Reference:

Neetu Chaturvedi, Erik Hsiao, Darrell Velegol, Seong H. Kim. Maskless Fabrication of Nanowells Using Chemically Reactive Colloids. Nano Letters, 2011; 11 (2): 672 DOI: 10.1021/nl1037984

New shapes of microcompartments: Molecular shells that encapsulate cellular components

In nature and engineering, microcompartments -- molecular shells made of proteins that can encapsulate cellular components -- provide a tiny home for important reactions. In bacterial organelles, for example, microcompartments known as carboxysomes trap carbon dioxide and convert it into sugar as an energy source.

These shells naturally buckle into a specialized 20-sided shape called an icosahedron. But now researchers at Northwestern University's McCormick School of Engineering and Applied Science have discovered and explored new shapes of microcompartment shells. Understanding just how these shells form could lead to designed microreactors that mimic the functions of these cell containers or deliver therapeutic materials to cells at specific targeted locations.

The research, led by Monica Olvera de la Cruz, professor of materials science and chemical and biological engineering and chemistry, with Graziano Vernizzi, research assistant professor, and research associate Rastko Sknepnek, was recently published in the Proceedings of the National Academy of Sciences.

Olvera de la Cruz and her group knew how shells made up of just one structural unit worked -- their elasticity and rigidity cause them to naturally buckle into icosahedra. But they began considering how to create heterogenous shells by using more than one component. Using physical concepts, mathematical analysis, and running simulations, they formulated a new model for the spontaneous faceting of shells.

"The question was: if a shell is made up of components that have different rigidities or different mechanical properties, what would be the shape it takes?" Olvera de la Cruz said.

The only faceted shape previously known for molecular closed shells, such as viruses and fullerenes, was the icosahedron. But Olvera de la Cruz and her colleagues discovered that when a shell is made up of two components with different elasticities, they buckle into many different shapes, including dodecahedra (12 sides) and octahedra (8 sides) and irregular polyhedra, which surfaces are "decorated" by the natural segregation of components to yield the lowest energy conformation.

Some of these shapes had been seen in nature before -- sometimes in the bacterial organelles' carboxysomes -- but they were just called "quasi-icosahedra" because nobody knew how to characterize them and how they worked. Armed with their model, however, engineers could now potentially design shells to perform specific tasks.

"If you just want to pack something into a shell, you use a sphere," she said. "But if you want to create a shell that has intelligence and can fit somewhere perfectly because it is decorated with the right proteins, then you can use different shapes."

These designed shells could act as containers or microreactors within the body. "It's a very efficient way to deliver something," she said.

Next the group hopes to determine how general their model is and continue researching how different shapes are made.

"I think it can open a new field of research," Olvera de la Cruz said.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

Journal Reference:

G. Vernizzi, R. Sknepnek, M. Olvera de la Cruz. Platonic and Archimedean geometries in multicomponent elastic membranes. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1012872108

3-D nanoparticle in atomic resolution

In chemical terms, nanoparticles have different properties from their "big brothers and sisters:" They have a large surface area in relation to their tiny mass and at the same time a small number of atoms. This can produce quantum effects that lead to altered material properties. Ceramics made of nanomaterials can suddenly become bendy, for instance, or a gold nugget is gold-coloured while a nanosliver of it is reddish.

New method developed

The chemical and physical properties of nanoparticles are determined by their exact three-dimensional morphology, atomic structure and especially their surface composition. In a study initiated by ETH Zurich scientist Marta Rossell and Empa researcher Rolf Erni, the 3D structure of individual nanoparticles has now successfully been determined on the atomic level. The new technique could help improve our understanding of the characteristic of nanoparticles, including their reactivity and toxicity.

Gentle imaging processing

For their electron-microscopic study, which was published recently in the journal Nature, Rossell and Erni prepared silver nanoparticles in an aluminium matrix. The matrix makes it easier to tilt the nanoparticles under the electron beam in different crystallographic orientations whilst protecting the particles from damage by the electron beam. The basic prerequisite for the study was a special electron microscope that reaches a maximum resolution of less than 50 picometres. By way of comparison: the diameter of an atom measures about one Angström, i.e. 100 picometres.

To protect the sample further, the electron microscope was set up in such a way as to also yield images at an atomic resolution with a lower accelerating voltage, namely 80 kilovolts. Normally, this kind of microscope -- of which there are only a few in the world -- works at 200 -- 300 kilovolts. The two scientists used a microscope at the Lawrence Berkeley National Laboratory in California for their experiments. The experimental data was complemented with additional electron-microscopic measurements carried out at Empa.

Sharper images

On the basis of these microscopic images, Sandra Van Aert from the University of Antwerp created models that "sharpened" the images and enabled them to be quantified: the refined images made it possible to count the individual silver atoms along different crystallographic directions.

For the three-dimensional reconstruction of the atomic arrangement in the nanoparticle, Rossell and Erni eventually enlisted the help of the tomography specialist Joost Batenburg from Amsterdam, who used the data to tomographically reconstruct the atomic structure of the nanoparticle based on a special mathematical algorithm. Only two images were sufficient to reconstruct the nanoparticle, which consists of 784 atoms. "Up until now, only the rough outlines of nanoparticles could be illustrated using many images from different perspectives," says Marta Rossell. Atomic structures, on the other hand, could only be simulated on the computer without an experimental basis.

"Applications for the method, such as characterising doped nanoparticles, are now on the cards," says Rolf Erni. For instance, the method could one day be used to determine which atom configurations become active on the surface of the nanoparticles if they have a toxic or catalytic effect. Rossell stresses that in principle the study can be applied to any type of nanoparticle. The prerequisite, however, is experimental data like that obtained in the study.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by Swiss Federal Laboratories for Materials Science and Technology (EMPA). The original article was written by Simone Ulmer/ETH Life.

Journal Reference:

Sandra Van Aert, Kees J. Batenburg, Marta D. Rossell, Rolf Erni, Gustaaf Van Tendeloo. Three-dimensional atomic imaging of crystalline nanoparticles. Nature, 2011; 470 (7334): 374 DOI: 10.1038/nature09741