Tag Archives: AIDS

Bee venom, HIV (human immunodeficiency virus), and targeted nanoparticles

Researchers at Washington University School of Medicine in St Louis (Missouri, US) have found a way to use nanoparticles impregnated with bee venom to hopelessly damage HIV (human immunodeficiency virus) in laboratory tests, according to a Mar. 7, 2013 news release on EurekAlert,

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.

 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.  Credit: Joshua L. Hood, MD, PhD (downloaded from: http://news.wustl.edu/news/Pages/25061.aspx

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. Credit: Joshua L. Hood, MD, PhD (downloaded from: http://news.wustl.edu/news/Pages/25061.aspx

Dexter Johnson in his Mar. 8, 2013 posting on Nanoclast (IEEE [Institute of Electrical and Electronics Engineers] blog) contextualizes this research with links to other related research along with his comments about this latest work (Note: A link has been removed),

The research, which was published in the journal Antiviral Therapy (“Cytolytic nanoparticles attenuate HIV-1 infectivity”), employed a nanoparticle that had previously been abandoned when it proved ineffective for delivering oxygen to blood cells. But in its new role, carrying the toxin melittin, a poison found in bee venom, it is extremely effective at breaking down the essential structure of HIV.

The Washington University in Saint Louis Mar. 7, 2013 news release (and origin for EurekAlert news release) written by Julia Evangelou Strait provides details about the research,

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.

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.

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.

Here’s a citation and link to the paper,

Joshua L Hood, Andrew P Jallouk, Nancy Campbell, Lee Ratner, Samuel A Wickline. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antiviral Therapy. Vol. 19: 95 – 103. 2013

The article is behind a paywall.

Zimbabwe and its international nanotechnology center, ZINC

A Sept.24, 2012 news item on Nanowerk provides information about a new nanotechnology center in Zimbabwe,

With 14 percent of Zimbabwe’s population living with HIV/AIDS and tuberculosis as a co-infection, the need for new drugs and new formulations of available treatments is crucial.

To address these issues, two of the University at Buffalo’s [UB] leading research centers, the Institute for Lasers, Photonics and Biophotonics (ILPB), and the New York State Center of Excellence in Bioinformatics and Life Sciences have signed on to launch the Zimbabwe International Nanotechnology Center (ZINC) — a national nanotechnology research program — with the University of Zimbabwe (UZ) and the Chinhoyi University of Technology (CUT).

This collaborative program will initially focus on research in nanomedicine and biosensors at UZ and energy at CUT. ZINC has grown out of the NIH [US National Institute of Health] Fogarty International Center, AIDS International Training and Research Program (AITRP) that was awarded to UB and UZ in 2008 to conduct HIV research training and build research capacity in Zimbabwe and neighboring countries in southern Africa.

I decided to find out more about Zimbabwe and found a map and details in a Wikipedia essay,

Location of Zimbabwe within the African Union (accessed Sept. 24, 2012 from the Wikipedia essay on Zimbabwe)

Zimbabwe (… officially the Republic of Zimbabwe) is a landlocked country located in Southern Africa, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest (making this area a quadripoint) and Mozambique to the east. The capital is Harare. Zimbabwe achieved recognised independence from Britain in April 1980, following a 14-year period as an unrecognised state under the predominantly white minority government of Rhodesia, which unilaterally declared independence in 1965. Rhodesia briefly reconstituted itself as black-majority ruled Zimbabwe Rhodesia in 1979, but this order failed to gain international acceptance.

Zimbabwe has three official languages: English, Shona and Ndebele.

Getting back to Zimbabwe, Alan on the Science Business website posted on Sept. 24, 2012 about ZINC and the partnership (excerpted from the posting),

University at Buffalo in New York and two universities in the southern African nation of Zimbabwe will collaborate on a new nanotechnology research program in pharmacology. University of Zimbabwe in Harare and the Chinhoyi University of Technology in Mashonaland West, working with Buffalo’s Institute for Lasers, Photonics, and Biophotonics, along with New York State Center of Excellence in Bioinformatics and Life Sciences also on the Buffalo campus, will establish the Zimbabwe International Nanotechnology Center (ZINC).

ZINC aims to develop an international research and training capability in nanotechnology that advances the field as contributor to Zimbabwe’s economic growth. The collaboration is expected to focus on research in nanomedicine and biosensors for health care at University of Zimbabwe, while the Chinhoyi University of Technology partnership will conduct research related to energy.

The University of Buffalo Sept. 24, 2012 news release provides more details,

The UB ILPB and TPRC [Translational Pharmacy Research Core] collaboration recognized that the fields of pharmacology and therapeutics have increasingly developed links with emerging areas within the field of nanosciences in an attempt to develop tissue/organ targeted strategies that will lead to disease treatment and eradication. Research teams will focus on emerging technologies, initially focused in nanobiotechnology and nanomedicine for health care.

“Developing nanoformulations for HIV and tuberculosis diagnostics and therapeutics, as well as new tuberculosis drug development, are just a few of the innovative strategies to address these co-infections that this research collaboration can provide,” said Morse [Gene D. Morse, PharmD, Professor of Pharmacy Practice, associate director of the New York State Center of Excellence in Bioinformatics and Life Sciences and director of the Translational Pharmacy Research Core {TPRC}].

“In addition, the development of new nanotechnology-related products will jumpstart the economy and foster new economic initiatives in Zimbabwe that will yield additional private-public partnerships.”

Morse says that the current plans for a “Center of Excellence” in clinical and translational pharmacology in Harare at UZ will create a central hub in Africa, not just for Zimbabwe but for other countries to gain new training and capacity building in many exciting aspects of nanotechnology as well.

Good luck to ZINC and its partners!

University of Liverpool announces work on HIV/AIDS nanomedicines

Given that Vancouver (Canada) is a world centre for HIV/AIDS  research (courtesy of Dr. Julio Montaner‘s work), the Aug. 30, 2012 news item on Nanowerk  about nanomedicines being developed at the University of Liverpool, which are less toxic therapeutic alternatives to current HIV/AIDS medications, caught my eye. From the news item,

Scientists at the University of Liverpool are leading a £1.65 million project to produce and test the first nanomedicines for treating HIV/AIDS.

There aren’t many details about how they are going to produce these nanomedicines other than what’s in these paragraphs in the Aug. 30, 2012 University of Liverpool news release,

The research project, funded by the [UK] Engineering and Physical Sciences Research Council (EPSRC), aims to produce cheaper, more effective medicines which have fewer side effects and are easier to give to newborns and children.

The new therapy options were generated by modifying existing HIV treatments, called antiretrovirals (ARVs). The University has recently produced ARV drug particles at the nanoscale which potentially reduce the toxicity and variability in the response different patients have to therapies. Drug nanoparticles have been shown to allow smaller doses in other disease areas which opens up possibilities to reduce drug side-effects and the risk of drug resistance. Nanoscale objects are less than one micron in size – a human hair is approximately 80 microns in diameter.

If I read the news release for this project rightly, there aren’t any immediate plans for making these nanomedicines widely available for treatment (from the University of Liverpool news release),

The project aims to deliver highly valuable data within three years and provide a platform for continual development and testing during that time

Elsewhere in the news release they do mention clinical trials,

Professor Andrew Owen, from the University’s Department of Molecular and Clinical Pharmacology, added: “We have integrated an assessment of pharmacology and safety early in the research and this has allowed us to rapidly progress lead options for clinical trials. The work has been conducted with the Medical Research Council (MRC) Centre for Drug Safety Science also based at the University.”

“Our data so far looks really exciting, offering the potential to reduce the doses required to control the HIV virus.  This work builds on initiatives by Médecins Sans Frontières and other groups to seek ways to improve ARV therapy and could have real benefits for the safety of ARVs globally. Importantly we also hope to reduce the costs of therapy for resource-limited countries where the burden of disease is highest.”

Interestingly, the other mention of taking this medicine into the field is in a  photo caption for the research team’s other featured member,

Professor Steve Rannard: “This project is the first step towards taking nanomedicine options out of our labs and into the clinic”

Good luck to them all!

French scientists focus optical microscopes down to 30 nm

In fact, the French scientists are using two different imaging techniques to arrive at a resolution of 30 nm for their optical microscopes, according to the May 18, 2012 news item on Nanowerk.

Researchers from the Institut Pasteur and CNRS [Centre national de la recherche scientifique] have set up a new optical microscopy approach that combines two recent imaging techniques in order to visualize molecular assemblies without affecting their biological functions, at a resolution 10 times better than that of traditional microscopes. Using this approach, they were able to observe the AIDS virus and its capsids (containing the HIV genome) within cells at a scale of 30 nanometres, for the first time with light.

More specifically,

A study coordinated by Dr Christophe Zimmer (Institut Pasteur/CNRS), in collaboration with Dr Nathalie Arhel within the lab headed by Pr Pierre Charneau (Institut Pasteur/CNRS), shows that the association of two recent imaging techniques helps obtain unique images of molecular assemblies of HIV-1 capsids, with a resolution around 10 times better than that of traditional microscopes. This new approach, which uses super-resolution imaging and FlAsH labeling, does not affect the virus’ ability to self-replicate. It represents a major step forward in molecular biology studies, enabling the visualisation of microbial complexes at a scale of 30 nm without affecting their function.

The newly developed approach combines super-resolution PALM imaging and fluorescent FlAsH labeling. PALM imaging relies on the acquisition of thousands of low-resolution images, each of which showing only a few fluorescent molecules. The molecular positions are then calculated with high accuracy by computer programs and compiled into a single high-resolution image. FlAsH labeling involves the insertion of a 6-amino-acid peptide into the protein of interest. The binding of the FlAsH fluorophore to the peptide generates a fluorescent signal, thereby enabling the visualization of the protein. For the first time, researchers have combined these two methods in order to obtain high-resolution images of molecular structures in either fixed or living cells.

The researchers have supplied an image illustrating the difference between the conventional and new techniques will allow them to view (from the May 16, 2012 press release  [communiqué de presses] on the CNRS website),

© Institut Pasteur Reconstruction optique super-résolutive de la morphologie du VIH. L'image du dessous montre la distribution moyenne de l'enzyme intégrase observée par FlAsH-PALM. La résolution de cette technique (~30 nm) permet de retrouver la taille et la forme conique de la capside. Pour comparaison, la résolution de la microscopie conventionnelle (~200-300 nm), illustrée par l'image du dessus, ne permet pas une description détaillée de cette structure.

The conventional 200 – 300 nm resolution is shown at the top while the new 30 nm resolution achieved by combining the new techniques is shown below. This new technique has already allowed scientists to disprove a popular theory about the AIDS virus, from the May 18, 2012 news item on Nanowerk,

This new method has helped researchers visualise the AIDS Virus and localise its capsids in human cells, at a scale of 30 nm. Capsids are conical structures which contain the HIV genome. These structures must dismantle in order for the viral genome to integrate itself into the host cell’s genome. However, the timing of this disassembly has long been debated. According to a prevailing view, capsids disassemble right after infection of the host cell and, therefore, do not play an important role in the intracellular transport of the virus to the host cell’s nucleus. However, the results obtained by the researchers of the Institut Pasteur and CNRS indicate that numerous capsids remain unaltered until entry of the virus into the nucleus, confirming and strengthening earlier studies based on electron microscopy. Hence, capsids could play a more important role than commonly assumed in the replication cycle of HIV.

I gather excitement about this development is high as the scientists are suggesting that ‘microscopy’ could be known as ‘nanoscopy’ in the future.