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Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease

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Home > Press > Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease

Abstract:
– Serum Z-AAT reductions of 86-93%

– All patients demonstrated greater than 80% reduction in liver Z-AAT monomer

– 3 of 4 patients had a decrease in liver globule involvement

– 3 of 4 patients demonstrated reductions in Z-AAT polymer with a range of 68-97%

– All patients showed ALT reductions ranging from 36-66%

Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease


Pasadena. CA | Posted on November 13th, 2020

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced positive interim clinical data from AROAAT2002, an open-label Phase 2 clinical study of ARO-AAT, the company’s second-generation investigational RNA interference (RNAi) therapeutic being developed as a treatment for the rare genetic liver disease associated with alpha-1 antitrypsin deficiency (AATD). The data demonstrate that three doses of ARO-AAT over 24-weeks resulted in consistent reductions of the disease-causing mutant Z protein (Z-AAT) and improvements in clinically relevant biomarkers of liver disease. The results were presented in a late-breaking poster at The Liver Meeting Digital Experience, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD).

A copy of the poster may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: “These data presented at AASLD strongly suggest that ARO-AAT is doing what it’s designed to do, which is reduce the production of the misfolded mutant Z-AAT protein. Moreover, these compelling results indicate that the liver may have the ability to clear out accumulated Z-AAT and begin to heal itself faster than anticipated. Importantly, we saw reductions in serum Z-AAT and liver Z-AAT which led to improvements in multiple markers, such as liver globules, ALT/GGT and Pro-C3. These are all positive indications of a strong pharmacodynamic response and improvement in liver health, following just three doses of ARO-AAT. We anticipate data from additional patient cohorts will be available in the coming months, which will be included in our planned discussions with the U.S. Food and Drug Administration and other regulatory agencies, aimed at exploring areas where the ARO-AAT program could potentially be streamlined and accelerated.”

In the AROAAT2002 study, four patients with homozygous PiZZ alpha-1 antitrypsin deficiency and evidence of fibrosis at screening, each received three doses of ARO-AAT on week 0, 4, and 16. Liver biopsies were performed at screening and at week 24. Assessments included safety (including pulmonary function tests), changes in serum Z-AAT, liver Z-AAT, ALT, GGT, Pro-C3, liver elastography (FibroScan®), and liver globule assessment. Additional histologic adjudication is ongoing.

Key data presented include the following:

Pharmacodynamic Response at 24 weeks

Serum Z-AAT reductions were 86-93%
Total intra-hepatic Z-AAT reductions were 72-95%
All patients demonstrated greater than 80% reduction in liver Z-AAT monomer (soluble)
3 of 4 patients demonstrated reductions in Z-AAT polymer (insoluble) with a range of 68-97%
3 of 4 patients had a decrease in liver globule involvement and 1 subject remained unchanged
All patients showed reductions in ALT (range 36-66%) and in GGT (range 43-58%)
3 of 4 patients demonstrated a substantial reduction of greater than 20% in FibroScan® values
3 of 4 patients showed greater than 30% reduction in serum Pro-C3, a marker of fibrogenesis
Safety

Overall, ARO-AAT 200 mg as a subcutaneous injection was well tolerated in PiZZ AATD subjects
One treatment emergent SAE of Epstein bar virus related myocarditis was reported
No treatment emergent AEs related to change in pulmonary status or pulmonary function were reported
No clinically meaningful changes in ppFEV1 from baseline to Week 24 were observed
In October 2020, Arrowhead and Takeda Pharmaceutical Company Limited announced a collaboration and licensing agreement to develop ARO-AAT. Under the terms of the agreement, Arrowhead and Takeda will co-develop ARO-AAT which, if approved, will be co-commercialized in the U.S. under a 50/50 profit-sharing structure. Outside the U.S., Takeda will lead the global commercialization strategy and receive an exclusive license to commercialize ARO-AAT with Arrowhead eligible to receive tiered royalties of 20-25% on net sales. Arrowhead will receive an upfront payment of $300 million and is eligible to receive potential development, regulatory and commercial milestones up to $740 million. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino Antitrust Improvements Act of 1976 in the U.S.

AROAAT2002 (NCT03946449) is a pilot open-label, multi-dose, Phase 2 study to assess the response to ARO-AAT in approximately 16 patients with AATD associated liver disease and baseline liver fibrosis who will be enrolled in three cohorts. All eligible participants will require a pre-dose biopsy and an end of study biopsy. Treated participants will also be offered the opportunity to continue treatment in an open-label extension (OLE). Including the OLE, interim assessments will be made after 6 months and 18 months (cohorts 1, 1b), and 12 months and 24 months (cohort 2) of treatment with ARO-AAT. Arrowhead is also evaluating ARO-AAT in the ongoing SEQUOIA Phase 2/3 trial, which began in August 2019.

####

About Arrowhead Pharmaceuticals, Inc.
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts .

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

For more information, please click here

Contacts:
Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400

Investors:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
www.lifesciadvisors.com

Media:
LifeSci Communications, LLC
Josephine Belluardo, Ph.D.
646-751-4361
www.lifescicommunications.com

Copyright © Arrowhead Pharmaceuticals, Inc.

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Nano Technology

An ionic forcefield for nanoparticles: Tunable coating allows hitch-hiking nanoparticles to slip past the immune system to their target

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Home > Press > An ionic forcefield for nanoparticles: Tunable coating allows hitch-hiking nanoparticles to slip past the immune system to their target

An SEM image of the nanoparticles on the red blood cell CREDIT
(Image courtesy of Eden Tanner/ Harvard SEAS)
An SEM image of the nanoparticles on the red blood cell CREDIT
(Image courtesy of Eden Tanner/ Harvard SEAS)

Abstract:
Nanoparticles are promising drug delivery tools, offering the ability to administer drugs directly to a specific part of the body and avoid the awful side effects so often seen with chemotherapeutics.

An ionic forcefield for nanoparticles: Tunable coating allows hitch-hiking nanoparticles to slip past the immune system to their target


Cambridge, MA | Posted on November 27th, 2020

But there’s a problem. Nanoparticles struggle to get past the immune system’s first line of defense: proteins in the blood serum that tag potential invaders. Because of this, only about 1 percent of nanoparticles reach their intended target.

“No one escapes the wrath of the serum proteins,” said Eden Tanner, a former postdoctoral fellow in bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

Now, Tanner and a team of researchers led by Samir Mitragotri, the Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering at SEAS, have developed an ionic forcefield that prevents proteins from binding to and tagging nanoparticles.

In mouse experiments, nanoparticles coated with the ionic liquid survived significantly longer in the body than uncoated particles and, surprisingly, 50 percent of the nanoparticles made it to the lungs. It’s the first time that ionic liquids have been used to protect nanoparticles in the blood stream.

“The fact that this coating allows the nanoparticles to slip past serum proteins and hitch a ride on red blood cells is really quite amazing because once you are able to fight the immune system effectively, lots of opportunities open up,” said Mitragotri, who is also a Core Faculty Member of Harvard’s Wyss Institute for Biologically Inspired Engineering

The research is published in Science Advances.

Ionic liquids, essentially liquid salts, are highly tunable materials that can hold a charge.

“We knew that serum proteins clear out nanoparticles in the bloodstream by attaching to the surface of the particle and we knew that certain ionic liquids can either stabilize or destabilize proteins,” said Tanner, who is now an Assistant Professor of Chemistry & Biochemistry at the University of Mississippi. “The question was, could we leverage the properties of ionic liquids to allow nanoparticles to slip past proteins unseen.”

“The great thing about ionic liquids is that every small change you make to their chemistry results in a big change in their properties,” said Christine Hamadani, a former graduate student at SEAS and first author of the paper. “By changing one carbon bond, you can change whether or not it attracts or repels proteins.”

Hamadani is currently a graduate student at Tanner’s lab at the University of Mississippi.

The researchers coated their nanoparticles with the ionic liquid choline hexenoate, which has an aversion to serum proteins. Once in the body, these ionic-liquid coated nanoparticles appeared to spontaneously attach to the surface of red-blood cells and circulate until they reached the dense capillary system of the lungs, where the particles sheared off into the lung tissue.

“This hitchhiking phenomenon was a really unexpected discovery,” said Mitragotri. “Previous methods of hitchhiking required special treatment for the nanoparticles to attach to red blood cells and even then, they only stayed at a target location for about six hours. Here, we showed 50 percent of the injected dose still in the lungs after 24 hours.”

The research team still needs to understand the exact mechanism that explains why these particles travel so well to lung tissue, but the research demonstrates just how precise the system can be.

“This is such a modular technology,” said Tanner, who plans to continue the research in her lab at University of Mississippi. “Any nanoparticle with a surface change can be coated with ionic liquids and there are millions of ionic liquids that can be tuned to have different properties. You could tune the nanoparticle and the liquid to target specific locations in the body.”

“We as a field need as many tools as we can to fight the immune system and get drugs where they need to go,” said Mitragotri. “Ionic liquids are the latest tool on that front.”

###

The research was co-authored by Morgan J. Goetz.

####

For more information, please click here

Contacts:
Leah Burrows

@hseas

Copyright © Harvard John A. Paulson School of Engineering and Applied Sciences

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One-way street for electrons: Scientists observe directed energy transport between neighbouring molecules in a nanomaterial

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Home > Press > One-way street for electrons: Scientists observe directed energy transport between neighbouring molecules in a nanomaterial

With the help of ultra-short laser pulses physicists at the University of Oldenburg study the ultra-fast processes occuring in nanomaterials after the absorption of light. CREDIT
University of Oldenburg
With the help of ultra-short laser pulses physicists at the University of Oldenburg study the ultra-fast processes occuring in nanomaterials after the absorption of light. CREDIT
University of Oldenburg

Abstract:
Whether in solar cells, in photosynthesis or in the human eye: when light falls on the material, a green leaf or the retina, certain molecules transport energy and charge. This ultimately leads to the separation of charges and the generation of electricity. Molecular funnels, so-called conical intersections, ensure that this transport is highly efficient and directed.

One-way street for electrons: Scientists observe directed energy transport between neighbouring molecules in a nanomaterial


Oldenburg, Germany | Posted on November 27th, 2020

An international team of physicists has now observed that such conical intersections also ensure a directed energy transport between neighbouring molecules of a nanomaterial. Theoretical simulations have confirmed the experimental results. Until now, scientists had observed this phenomenon only within one molecule. In the long term, the results could help to develop more efficient nanomaterials for organic solar cells, for example. The study, led by Antonietta De Sio, University of Oldenburg, and Thomas Frauenheim, University of Bremen, Germany, was published in the current issue of the scientific journal Nature Nanotechnology.

Photochemical processes play a major role in nature and in technology: when molecules absorb light, their electrons transit to an excited state. This transition triggers extremely fast molecular switching processes. In the human eye, for example, the molecule rhodopsin rotates in a certain way after absorbing light and thus ultimately triggers an electrical signal – the most elementary step in the visual process.

First experimental evidence for conical intersections between molecules

The reason for this is a special property of rhodopsin molecules, explains Christoph Lienau, professor of ultrafast nano-optics at the University of Oldenburg and co-author of the study: “The rotation process always takes place in a similar way, although from a quantum mechanical point of view there are many different possibilities for the molecular movement”.

This is due to the fact that the molecule has to funnel through a conical intersection during the rotation process, as a research team demonstrated experimentally in visual pigment in 2010: “This quantum mechanical mechanism functions like a one-way street in the molecule: It channels the energy in a certain direction with a very high probability,” explains Lienau.

The research team led by Antonietta De Sio, senior scientist in the research group Ultrafast Nano-optics at the University of Oldenburg, and Thomas Frauenheim, professor of Computational Materials Science at the University of Bremen, has now observed such a one-way street for electrons in a nanomaterial. The material has been synthesized by colleagues from the University of Ulm, Germany, and is already used in efficient organic solar cell devices.

“What makes our results special is that we have experimentally demonstrated conical intersections between neighbouring molecules for the first time,” explains De Sio. Until now, physicists worldwide had only observed the quantum mechanical phenomenon within a single molecule and only speculated that there might also be conical intersections between molecules lying next to each other.

Theoretical calculations support experimental data

De Sio’s Team has discovered this one-way street for electrons by using methods of ultrafast laser spectroscopy: The scientists irradiate the material with laser pulses of only a few femtoseconds in duration. One femtosecond is a millionth of a billionth of a second. The method enables the researchers to record a kind of film of the processes that take place immediately after the light reaches the material. The group was able to observe how electrons and atomic nuclei moved through the conical intersection.

The researchers found that a particularly strong coupling between the electrons and specific nuclear vibrations helps to transfer energy from one molecule to another as if on a one-way street. This is exactly what happens in the conical intersections. “In the material we studied, it took only about 40 femtoseconds between the very first optical excitation and the passage through the conical intersection,” says De Sio.

In order to confirm their experimental observations, the researchers from Oldenburg and Bremen also collaborated with theoretical physicists from the Los Alamos National Laboratory, New Mexico, USA, and CNR-Nano, Modena, Italy. “With their calculations, they have clearly shown that we have interpreted our experimental data correctly,” explains De Sio.

The Oldenburg researchers are not yet able to estimate in detail the exact effect of these quantum mechanical one-way streets on future applications of molecular nanostructures. However, in the long term the new findings could help to design novel nanomaterials for organic solar cells or optoelectronic devices with improved efficiencies, or to develop artificial eyes from nanostructures.

####

For more information, please click here

Contacts:
Antonietta De Sio
49-441-798-3490

Copyright © University of Oldenburg

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Quantum nanodiamonds may help detect disease earlier: The quantum sensing abilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study led by UCL research

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Home > Press > Quantum nanodiamonds may help detect disease earlier: The quantum sensing abilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study led by UCL research

An artist's conception of nanodiamonds used for in vitro diagnostics. CREDIT
Ella Maru Studio/ UCL
An artist’s conception of nanodiamonds used for in vitro diagnostics. CREDIT
Ella Maru Studio/ UCL

Abstract:
The quantum sensing abilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study led by UCL researchers in the i-sense McKendry group.

Quantum nanodiamonds may help detect disease earlier: The quantum sensing abilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study led by UCL research


London, UK | Posted on November 27th, 2020

Paper-based lateral flow tests work the same way as a pregnancy test in that a strip of paper is soaked in a fluid sample and a change in colour – or fluorescent signal – indicates a positive result and the detection of virus proteins or DNA. They are widely used to detect viruses ranging from HIV to SARS-CoV-2 (lateral flow tests for Covid-19 are currently being piloted across England) and can provide a rapid diagnosis, as the results do not have to be processed in a lab.

The new research, published in Nature, found that low-cost nanodiamonds could be used to signal the presence of an HIV disease marker with a sensitivity many thousands of times greater than the gold nanoparticles widely used in these tests.

This greater sensitivity allows lower viral loads to be detected, meaning the test could pick up lower levels of disease or detect the disease at an earlier stage, which is crucial for reducing transmission risk of infected individuals and for effective treatment of diseases such as HIV.

The research team are working on adapting the new technology to test for COVID-19 and other diseases over the coming months. A key next step is to develop a hand-held device that can “read” the results, as the technique was demonstrated using a microscope in a laboratory. Further clinical evaluation studies are also planned.

Lead author Professor Rachel McKendry, Professor of Biomedical Nanotechnology at UCL and Director of i-sense EPSRC IRC, said: “Our proof-of-concept study shows how quantum technologies can be used to detect ultralow levels of virus in a patient sample, enabling much earlier diagnosis.

“We have focused on the detection of HIV, but our approach is very flexible and can be easily adapted to other diseases and biomarker types. We are working on adapting our approach to COVID-19. We believe that this transformative new technology will benefit patients and protect populations from infectious diseases.”

The researchers made use of the quantum properties of nanodiamonds manufactured with a precise imperfection. This defect in the highly regular structure of a diamond creates what is called a nitrogen-vacancy (NV) centre. NV centres have many potential applications, from fluorescent biomarking for use in ultra-sensitive imaging to information processing qubits in quantum computing.

The NV centres can signal the presence of an antigen or other target molecule by emitting a bright fluorescent light. In the past, fluorescent markers have been limited by background fluorescence, either from the sample or the test strip, making it harder to detect low concentrations of virus proteins or DNA that would indicate a positive test. However, the quantum properties of fluorescent nanodiamonds allow their emission to be selectively modulated, meaning the signal can be fixed at a set frequency using a microwave field and can be efficiently separated from the background fluorescence, addressing this limitation.

The optical results showed up to a five orders of magnitude (100,000 times) improvement in sensitivity compared to gold nanoparticles (that is, a much lower number of nanoparticles were required to generate a detectable signal). With the inclusion of a short 10-minute constant-temperature amplification step, in which copies of the RNA were multiplied, the researchers were able to detect HIV RNA at the level of a single molecule in a model sample.

The work was demonstrated in a laboratory setting but the team hopes to develop the tests so that the results could be read with a smartphone or portable fluorescence reader. This means that the test could, in future, be performed in low-resource settings, making it more accessible to users.

First author Dr Ben Miller (i-sense Postdoctoral Research Associate at the London Centre for Nanotechnology at UCL) said: “Paper-based lateral flow tests with gold nanoparticles do not require laboratory analysis, making them particularly useful in low resource settings and where access to healthcare is limited. They are low cost, portable, and user friendly.

“However, these tests currently lack the sensitivity to detect very low levels of biomarkers. By replacing commonly used gold nanoparticles with fluorescent nanodiamonds in this new design, and selectively modulating their (already bright) emission of light, we have been able to separate their signal from the unwanted background fluorescence of the test strip, dramatically improving sensitivity.”

Co-author Professor John Morton, Director of UCL’s Quantum Science and Technology Institute (UCLQ), said: “This interdisciplinary collaboration between UCLQ and the i-sense team in the LCN is a fantastic illustration of how foundational work on quantum systems, such as NV centre in diamond, can evolve from the lab and play a crucial role in real-world applications in sensing and diagnostics. Researchers at UCLQ are exploring and enabling the impact of these and other quantum technologies by working with industry and other academic research groups.”

###

The study was carried out by an interdisciplinary team of i-sense researchers from UCL, UCLH, and University of Oxford, led by the London Centre for Nanotechnology at UCL. i-sense is an Interdisciplinary Research Collaboration (IRC) funded by the UK Engineering and Physical Sciences Research Council (EPSRC).

This work was funded by the UK EPSRC, Royal Society, London Centre for Nanotechnology, H2020 European Research Council, the UCLH NHS Foundation Trust and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

####

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Contacts:
Mark Greaves

@uclnews

Copyright © University College London

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Phytoplankton disturbed by nanoparticles: Due to its antibacterial properties, nanosilver is used in a wide range of products from textiles to cosmetics; but nanosilver if present at high concentrations also disrupts the metabolism of algae that are essential for the aquatic food

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Home > Press > Phytoplankton disturbed by nanoparticles: Due to its antibacterial properties, nanosilver is used in a wide range of products from textiles to cosmetics; but nanosilver if present at high concentrations also disrupts the metabolism of algae that are essential for the aquatic food

This nanoparticle disrupts the metabolism of algae. CREDIT
UNIGE/ Wei Liu
This nanoparticle disrupts the metabolism of algae. CREDIT
UNIGE/ Wei Liu

Abstract:
Products derived from nanotechnology are efficient and highly sought-after, yet their effects on the environment are still poorly understood. A research team from the University of Geneva (UNIGE), working in collaboration with the University of California at Santa Barbara, have investigated the effects of nanosilver, currently used in almost 450 products for its antibacterial properties, on the algae known as Poterioochromonas malhamensis. The results – published in the journal Scientific Reports – show that nanosilver and its derivative, ionic silver, disturb the alga’s entire metabolism. Its membrane becomes more permeable, the cellular reactive oxygen species increases and photosynthesis is less effective. The Swiss-American team was able to demonstrate for the first time the metabolic perturbations induced by nanosilver following its uptake in the food vacuoles of freshwater algae, paving the way for early detection of the metabolic changes before they express themselves physiologically.

Phytoplankton disturbed by nanoparticles: Due to its antibacterial properties, nanosilver is used in a wide range of products from textiles to cosmetics; but nanosilver if present at high concentrations also disrupts the metabolism of algae that are essential for the aquatic food


Geneva, Switzerland | Posted on November 27th, 2020

The nanosilver is used for its antibacterial properties and is employed in textiles and cosmetics, inter alia. In addition, the agro-food, biomedical and biopharmaceutical industry is interested in it for developing drugs, devices and pesticides. «Since nanosilver is designed to destroy, repel or render harmless noxious organisms such as bacteria, scientists have realised that it might also be harmful to organisms that are crucial to our environment,» begins Vera Slaveykova from the Department F.A. Forel for Environmental and Aquatic Sciences in UNIGE’s Faculty of Sciences. To assess the influence of nanotechnology products on phytoplankton and to evaluate the impacts on aquatic environment, the researcher team conducted a study on the alga Poterioochromonas malhamensis as a model phytoplankton species. «The phytoplankton are everywhere, in lakes and oceans,” continues Professor Slaveykova. «As a whole, phytoplankton generate almost half of the oxygen we breathe. And they have a second essential role, since they are at the base of the food chain. If they accumulate nanoparticles, these will be integrated into the aquatic food chain».

Multiple disturbances

The study led by Professor Slaveykova shows that treating the algae with nanosilver disrupts the metabolism of the amino acids that are vital for producing cellular proteins, the nucleotide metabolism that is important for genes, and fatty and tricarboxylic acids making up the membranes, as well as the photosynthesis and photorespiration elements.

The study results suggest that the silver ions released by the silver nanoparticles are the main toxicity factor. «The nanosilver is internalised in the algal cells by the phagocytotic mechanism used to supply cells with organic matter,» continues Professor Slaveykova. The study is the first to demonstrate that nanoparticles can follow such internalisation path in a species of phytoplankton. «These measurements were carried out in Geneva by Dr Liu using transmission electron microscopy. This entry mechanism is only known in Poterioochromonas malhamensis; it is still unknown if other phytoplankton species express it,» explains the Geneva researcher.

To finish demonstrating nanosilver’s toxicity, the international research team highlighted the fact that metabolic disturbances induce physiological dysfunctions. Professor Slaveykova observed lipid peroxidation leading to membrane permeabilization, increased oxidative stress and less efficient photosynthesis – and, it follows, reduced oxygen production.

An Approach That Needs to Be Implemented

The study underlines the full potential of metabolomics geared towards the molecular basis of the disruptions observed. «It’s a fundamental contribution to the field: although the metabolomics approaches are properly in place in medical and pharmaceutical sciences, it’s not at all the case for environmental toxicology where phytoplankton metabolomics is still in its infancy. The metabolomics is, therefore, a technique that offers the possibility of early detection of changes induced by a toxin, upstream of more global effects such as the alga growth inhibition and their impact on oxygen production. As it’s never easy to demonstrate the relationships between cause and effect in complex environment, it is now essential to use approaches like these.»

####

For more information, please click here

Contacts:
Vera I. Slaveykova
41-223-790-335

@UNIGEnews

Copyright © University of Geneva

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Source: http://www.nanotech-now.com/news.cgi?story_id=56450

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