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Posts Tagged ‘nanotechnology’

Nanotechnology against malaria parasites

December 13, 2014 Leave a comment

After maturation, malaria parasites (yellow) are leaving an infected red blood cell and are efficiently blocked by nanomimics (blue). (Fig: Modified with permission from ACS)

Malaria parasites invade human red blood cells, they then disrupt them and infect others. Researchers at the University of Basel and the Swiss Tropical and Public Health Institute have now developed so-called nanomimics of host cell membranes that trick the parasites. This could lead to novel treatment and vaccination strategies in the fight against malaria and other infectious diseases. Their research results have been published in the scientific journal ACS Nano.

For many infectious diseases no vaccine currently exists. In addition, resistance against currently used drugs is spreading rapidly. To fight these diseases, innovative strategies using new mechanisms of action are needed. The  Plasmodium falciparum that is transmitted by the Anopheles mosquito is such an example. Malaria is still responsible for more than 600,000 deaths annually, especially affecting children in Africa (WHO, 2012).

Artificial bubbles with receptors

Malaria parasites normally invade human red  in which they hide and reproduce. They then make the host cell burst and infect new cells. Using nanomimics, this cycle can now be effectively disrupted: The egressing parasites now bind to the nanomimics instead of the red blood cells.

Researchers of groups led by Prof. Wolfgang Meier, Prof. Cornelia Palivan (both at the University of Basel) and Prof. Hans-Peter Beck (Swiss TPH) have successfully designed and tested host cell nanomimics. For this, they developed a simple procedure to produce polymer vesicles – small artificial bubbles – with host cell receptors on the surface. The preparation of such polymer vesicles with water-soluble host receptors was done by using a mixture of two different block copolymers. In aqueous solution, the nanomimics spontaneously form by self-assembly.

Blocking parasites efficiently

Usually, the malaria parasites destroy their host cells after 48 hours and then infect new . At this stage, they have to bind specific host cell receptors. Nanomimics are now able to bind the egressing parasites, thus blocking the invasion of new cells. The parasites are no longer able to invade host cells, however, they are fully accessible to the immune system.

The researchers examined the interaction of nanomimics with malaria parasites in detail by using fluorescence and electron microscopy. A large number of nanomimics were able to bind to the parasites and the reduction of infection through the nanomimics was 100-fold higher when compared to a soluble form of the host cell receptors. In other words: In order to block all , a 100 times higher concentration of soluble host  is needed, than when the receptors are presented on the surface of nanomimics.

“Our results could lead to new alternative treatment and vaccines strategies in the future”, says Adrian Najer first-author of the study. Since many other pathogens use the same  receptor for invasion, the nanomimics might also be used against other . The research project was funded by the Swiss National Science Foundation and the NCCR “Molecular Systems Engineering”.

More information: Adrian Najer, Dalin Wu, Andrej Bieri, Françoise Brand, Cornelia G. Palivan, Hans-Peter Beck, and Wolfgang Meier. “Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites.” ACS Nano, Publication Date (Web): November 29, 2014 | DOI: 10.1021/nn5054206

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Nanomotors Steered Inside Living Human Cells For the First Time

March 13, 2014 1 comment

A group of researchers from Penn State have pushed the realm of possibilities for nanotechnology further as they have successfully steered a nanomotor inside of a human cell. This is the first time this feat has been accomplished. The team of chemists, biologist, and engineers was led by Tom Mallouk and has been published in Angewandte Chemie International Edition.

photo credit: Mallouk Lab/ Penn State

Nanomotors have been studied in vitro more more than a decade now. The hope is that eventually, they could be used inside of human cells for biomedical research. This nanotechnology could revolutionize drug delivery and even perform surgery in order to increase quality of life in the least invasive way possible. The earliest models were nonfunctional in biological fluid due to their fuel source. A huge breakthrough came later when the nanomotors were able to be powered externally via acoustic waves. The nanomotors used inside the human cells for the latest study were controlled by the ultrasonic waves as well as magnets.

The researchers used HeLa cells, derived from a long-lived line of cervical cancer cells, to study the nanomotors. Getting past the cell membrane was easy, as the cells ingested the nanomotors themselves. Once inside, the ultrasound was turned on and the nanomotors began to spin and move around the cell. If the signal was turned up even higher, the nanomotor can spin like a propeller, chopping up the organelles inside the cell. They were even able to puncture the cell membrane, finishing off the death sentence. Used at low powers, the nanomotor was able to move around the cell without causing any damage.

The addition of magnets gave an important advantage: steering. The motors are also able to be controlled individually, allowing the operator to take a much more targeted approach to killing diseased cells.

Ultimately, the researchers hope that one day the rocket-shaped gold nanorods will be able to move in an out of the cells without causing damage. The individual units could communicate with one another to target disease in the body, maximizing the efficacy of the treatment or even making the correct diagnosis. Working toward the goal of creating such advanced nanotechnology will not only push the boundaries of nanoengineering, but will increase our understanding of chemical and biological processes at the cellular level as well.

“The assembly of a rotating HeLa cell/gold rod aggregate at an acoustic nodal line in the xy plane. The video was taken under 500X overall magnification except for 00:23 – 00:32 and 01:16 – 01:42, where a 200X overall magnification was used.” Credit: Mallouk Lab, Penn State

“Very active gold nanorods internalized inside HeLa cells in an acoustic field. A demonstration of very active gold nanorods internalized inside HeLa cells in an acoustic field. This video was taken under 1000X magnification in the bright field, with most of the incoming light blocked at the aperture.” Credit: Mallouk Lab, Penn State

 

The above story is reprinted from materials provided by I F* Love Science.

Nanoparticles Laced With Bee Venom Selectively Destroy HIV Virus


Nanoparticles carrying a toxin found in bee venom can destroy human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS.

“Our hope is that in places where HIV is running rampant, people could use this gel as a preventive measure to stop the initial infection,” says Joshua L. Hood, MD, PhD, a research instructor in medicine.

The study appears in the current issue of Antiviral Therapy.

Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV, and other viruses. Large amounts of free melittin can cause a lot of damage. Indeed, in addition to anti-viral therapy, the paper’s senior author, Samuel A. Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences, has shown melittin-loaded nanoparticles to be effective in killing tumor cells.

Nanoparticles (purple) carrying melittin (green) fuse with HIV (small circles with spiked outer ring), destroying the virus’s protective envelope. Molecular bumpers (small red ovals) prevent the nanoparticles from harming the body’s normal cells, which are much larger in size.

The new study shows that melittin loaded onto these nanoparticles does not harm normal cells. That’s because Hood added protective bumpers to the nanoparticle surface. When the nanoparticles come into contact with normal cells, which are much larger in size, the particles simply bounce off. HIV, on the other hand, is even smaller than the nanoparticle, so HIV fits between the bumpers and makes contact with the surface of the nanoparticle, where the bee toxin awaits.

“Melittin on the nanoparticles fuses with the viral envelope,” Hood says. “The melittin forms little pore-like attack complexes and ruptures the envelope, stripping it off the virus.”

According to Hood, an advantage of this approach is that the nanoparticle attacks an essential part of the virus’ structure. In contrast, most anti-HIV drugs inhibit the virus’s ability to replicate. But this anti-replication strategy does nothing to stop initial infection, and some strains of the virus have found ways around these drugs and reproduce anyway.

“We are attacking an inherent physical property of HIV,” Hood says. “Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.”

Beyond prevention in the form of a vaginal gel, Hood also sees potential for using nanoparticles with melittin as therapy for existing HIV infections, especially those that are drug-resistant. The nanoparticles could be injected intravenously and, in theory, would be able to clear HIV from the blood stream.

“The basic particle that we are using in these experiments was developed many years ago as an artificial blood product,” Hood says. “It didn’t work very well for delivering oxygen, but it circulates safely in the body and gives us a nice platform that we can adapt to fight different kinds of infections.”

Since melittin attacks double-layered membranes indiscriminately, this concept is not limited to HIV. Many viruses, including hepatitis B and C, rely on the same kind of protective envelope and would be vulnerable to melittin-loaded nanoparticles.

While this particular paper does not address contraception, Hood says the gel easily could be adapted to target sperm as well as HIV. But in some cases people may only want the HIV protection.

“We also are looking at this for couples where only one of the partners has HIV, and they want to have a baby,” Hood says. “These particles by themselves are actually very safe for sperm, for the same reason they are safe for vaginal cells.”

While this work was done in cells in a laboratory environment, Hood and his colleagues say the nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

Journal referrence:

Hood JL, Jallouck AP, Campbell N, Ratner L, Wickline SA. Cytolytic nanoparticles attenuate HIV-1 infectivityAntiviral Therapy. Vol. 19: 95 – 103. 2013

Source:

Washington University in St. Louis