Novel Nanomedicine Inhibits Progression of Pancreatic Cancer in Mice – Tel Aviv University


Nanomedicine I download

Survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumor suppressant, Tel Aviv University researchers say

A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene — a gene that promotes the development of cancer — and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.

Nanomedicine III imagesThe study, which was published in Nature Communications, was led by Prof. Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr. Shay Eliyahu, both of Prof. Satchi-Fainaro’s multidisciplinary laboratory, in collaboration with Prof. Eytan Ruppin of TAU’s Computer Science Department and the University of Maryland and Prof. Iris Barshack and Dr. Talia Golan of Chaim Sheba Medical Center, Tel Hashomer.

Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within just a year of diagnosis. “Despite all the treatments afforded by modern medicine, some 75% of all pancreatic cancer patients die within 12 months of diagnosis, including many who die within just a few months,” Prof. Satchi-Fainaro says.

“But around seven percent of those diagnosed will survive more than five years. We sought to examine what distinguishes the survivors from the rest of the patients,” Prof. Satchi-Fainaro continues. “We thought that if we could understand how some people live several years with this most aggressive disease, we might be able to develop a new therapeutic strategy.”

Nanomedicine I downloadCalling a nano-taxi

The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumor suppressant, and PLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation made sense for such an aggressive cancer. But the team needed to see if the same was true in humans.

The scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients. The molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer.

The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues.

“We designed a nanocarrier to deliver two passengers: (1) miR-34a, which degrades hundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), that silences a single gene,” Prof. Satchi-Fainaro says. “These were delivered directly to the tumor site to change the molecular signature of the cancer cells, rendering the tumor dormant or eradicating it altogether.Nanomedicine II pancreatic-cancer-1140x641

“The nanoparticle is like a taxi carrying two important passengers,” Prof. Satchi-Fainaro continues. “Many oncology protocols are cocktails, but the drugs usually do not reach the tumor at the same time. But our ‘taxi’ kept the ‘passengers’ — and the rest of the body — safe the whole way, targeting only the tumor tissue. Once it ‘parked,’ an enzyme present in pancreatic cancer caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address — the tumor cells.”

Improving the odds

To validate their findings, the scientists injected the novel nanoparticles into pancreatic tumor-bearing mice and observed that by balancing these two targets — bringing them to a normal level by increasing their expression or blocking the gene responsible for their expression — they significantly prolonged the survival of the mice.

“This treatment takes into account the entire genomic pattern, and shows that affecting a single gene is not enough for the treatment of pancreatic cancer or any cancer type in general,” according to Prof. Satchi-Fainaro.

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Research for the study was funded by the European Research Council (ERC), Tel Aviv University’s Cancer Biology Research Center (CBRC) and the Israel Science Foundation (ISF).

American Friends of Tel Aviv University (AFTAU) supports Israel’s most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. For three years in a row, TAU ranked 9th in the world, and first in Israel, for alumni going on to become successful entrepreneurs backed by significant venture capital, a ranking that surpassed several Ivy League universities. To date, 2,400 patents have been filed out of the University, making TAU 29th in the world for patents among academic institutions.

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Light-activated Nanoparticles (Quantum Dots) can supercharge current antibiotics


QDs and Antibiotics CU 171004142650_1_540x360CU Boulder researcher Colleen Courtney (left) speaks with Assistant Professor Anushree Chatterjee (right) inside a lab in the BioFrontiers Institute.
Credit: University of Colorado Boulder

Light-activated nanoparticles, also known as quantum dots, can provide a crucial boost in effectiveness for antibiotic treatments used to combat drug-resistant superbugs such as E. coliand Salmonella, new University of Colorado Boulder research shows.

Multi-drug resistant pathogens, which evolve their defenses faster than new antibiotic treatments can be developed to treat them, cost the United States an estimated $20 billion in direct healthcare costs and an additional $35 billion in lost productivity in 2013.

CU Boulder researchers, however, were able to re-potentiate existing antibiotics for certain clinical isolate infections by introducing nano-engineered quantum dots, which can be deployed selectively and activated or de-activated using specific wavelengths of light.

Rather than attacking the infecting bacteria conventionally, the dots release superoxide, a chemical species that interferes with the bacteria’s metabolic and cellular processes, triggering a fight response that makes it more susceptible to the original antibiotic.

“We’ve developed a one-two knockout punch,” said Prashant Nagpal, an assistant professor in CU Boulder’s Department of Chemical and Biological Engineering (CHBE) and the co-lead author of the study. “The bacteria’s natural fight reaction [to the dots] actually leaves it more vulnerable.”

The findings, which were published today in the journal Science Advances, show that the dots reduced the effective antibiotic resistance of the clinical isolate infections by a factor of 1,000 without producing adverse side effects.

“We are thinking more like the bug,” said Anushree Chatterjee, an assistant professor in CHBE and the co-lead author of the study. “This is a novel strategy that plays against the infection’s normal strength and catalyzes the antibiotic instead.”

While other previous antibiotic treatments have proven too indiscriminate in their attack, the quantum dots have the advantage of being able to work selectively on an intracellular level. Salmonella, for example, can grow and reproduce inside host cells. The dots, however, are small enough to slip inside and help clear the infection from within.

“These super-resistant bugs already exist right now, especially in hospitals,” said Nagpal. “It’s just a matter of not contracting them. But they are one mutation away from becoming much more widespread infections.”

Overall, Chatterjee said, the most important advantage of the quantum dot technology is that it offers clinicians an adaptable multifaceted approach to fighting infections that are already straining the limits of current treatments.

“Disease works much faster than we do,” she said. “Medicine needs to evolve as well.”

Going forward, the researchers envision quantum dots as a kind of platform technology that can be scaled and modified to combat a wide range of infections and potentially expand to other therapeutic applications.

Story Source:

Materials provided by University of Colorado at Boulder. Original written by Trent Knoss. Note: Content may be edited for style and length.


Journal Reference:

  1. Colleen M. Courtney, Samuel M. Goodman, Toni A. Nagy, Max Levy, Pallavi Bhusal, Nancy E. Madinger, Corrella S. Detweiler, Prashant Nagpal, and Anushree Chatterjee. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generationScience Advances, 04 Oct 2017 DOI: 10.1126/sciadv.1701776

Tiny Nanoparticles Could Help Repair Damaged Brain And Nerve Cells


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When our brains develop problems, such as degenerative diseases or epilepsy, some of the trouble can be electrical. As nerve signals involve electrically charged particles moving around, medics often try to treat associated problems using implanted electrodes. But this is a clumsy and difficult approach. A much better idea could be to implant tiny structures deep in the brain to act almost as miniature electricians. It may sound like science fiction, but it is moving fast towards reality.

Attilio Marino and colleagues at the Smart Bio-Interfaces group at the Italian Institute of Technology in Pontedera are striving to bring the idea to the clinic. They summarise progress in the field in a news and opinions article in Nano Today.brain_header

Nanomaterials are showing great potential in biomedicine since they can interact precisely with living systems down to the level of cells, subcellular structures and even individual molecules,” says Marino.

Marino is most interested in ‘piezoelectric‘ materials, which can convert mechanical stimulation into electrical energy, or vice-versa. He is exploring using ultrasound to mechanically stimulate nanoparticles into creating electrical signals that may fix problems with brain cells.

He points out that ultrasound offers a way to get a signal deep into brain tissue without using invasive electrodes, which can cause other problems including inflammation. Some researchers try to get round these difficulties using stimulation with light, but light cannot penetrate very deeply so ultrasound is a better option.

The field is still in its early days. Researchers are mainly studying the effects of piezoelectric nanoparticles on cultured cells rather than in animals or people, but the results are promising. Marino’s team, for example, shows that using ultrasound to stimulate nanoparticles embedded in nerve cells can increase the sprouting of new cell-signalling appendages called axons. This is exactly the kind of effect that may one day repair degenerative brain disease.

“We used barium titanate nanoparticles and confirmed the effect was specifically due to the piezoelectricity of our materials,” says Marino.

Other researchers are working with the ‘stem cells‘ that can develop into a wide range of mature types of cell needed by the body. Some are finding that piezoelectric nanomaterials can stimulate stem cells to begin their transformation into a variety of functional cell types.

A long road of safety studies, animal tests and eventual clinical trials lies ahead. But Marino is optimistic, he concludes: “The preliminary successes strongly encourage us that our research is a realistic approach for use in clinical practice in the near future.”


You can read the article for free for a limited time:

Marino, A., et al.: “Piezoelectric nanotransducers: The future of neural stimulation,” Nano Today (2017)

Nanotechnology and Cardiovascular Nanomedicine


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Applications of various nano platforms in the prevention and treatment of cardiovascular disease. Nano platforms can target and break down coronary artery plaques and prevent injuries caused by stenosis or occlusion of arteries. Nanoparticulate systems can also reduce the adverse effects of reperfusion injuries and regenerate/salvage myocardium after MI, through sustained and targeted delivery of cells, biomolecules and paracrine factors. (© Nature Publishing Group) (click on image to enlarge)

Ischemic cardiomyopathy (CM) is the most common type of dilated cardiomyopathy. In Ischemic CM, the heart’s ability to pump blood is decreased because the heart’s main pumping chamber, the left ventricle, is enlarged, dilated and weak. This is caused by ischemia – a lack of blood supply to the heart muscle caused by coronary artery disease and heart attacks.

Treatment of ischemic CM is aimed at treating coronary artery disease, improving cardiac function and reducing heart failure symptoms. Patients usually take several medications to treat CM. Doctors also recommend lifestyle changes to decrease symptoms and hospitalizations and improve quality of life. In addition, devices and surgery may be advised.
“Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease,” says Morteza Mahmoudi, Director of and Principal Investigator at the NanoBio Interactions Laboratory at Tehran University of Medical Sciences. “Given the unique physical and chemical properties of nanostructured systems, nanoscience and nanotechnology have recently demonstrated the potential to overcome many of the limitations of cardiovascular medicine through the development of new pharmaceuticals, imaging reagents and modalities, and biomedical devices.”
Mahmoudi is first author of a review paper in Nature Nanotechnology (“Multiscale technologies for treatment of ischemic cardiomyopathy”), that covers the current state of the art in employing nanoparticulate systems either to inhibit or treat ischemic heart injuries caused by the stenosis or occlusion of coronary arteries.
The review provides a brief overview of recent advances in the use of nano platforms for early detection and treatment of coronary atherosclerosis to inhibit myocardial infarction (MI; heart attack). The authors also introduce new therapeutic opportunities in the regeneration/repair of ischemic myocardium using both nanoparticles and nanostructured biomaterials that can deliver therapeutic molecules and/or (stem) cells into hibernating myocardium.
The paper further provides an overview of recent advances in precise in vivo imaging of transplanted cells using bacterially developed nanoparticles and explain how these findings address crucial issues in in vivo cell monitoring and facilitate the clinical translation of cell therapies.
Finally, the authors examine the strengths and limitations of current approaches and discuss likely future trends in the application of nanotechnology to cardiovascular nanomedicine. Nano Cardio id48033
Here is a summary of the review, which offers an outline of critical issues and emerging developments in cardiac nanotechnology, which overall represent tremendous opportunities for advancing the field.

Diagnosis and treatment of coronary atherosclerosis

Nanoparticles have demonstrated potential in both detection and removal of atherosclerotic plaques. For instance, nanoparticles can deliver therapeutic biomolecules to the site of coronary atherosclerosis and shrink plaques by reducing inflammation (for example, by activation of pro-resolving pathways), and removing lipids and cholesterol crystals.
“The main limiting issue for design of safe and efficient nanoparticles for both prognosis and treatment of coronary atherosclerosis is our lack of a deep understanding of the biological identity of nanoparticles” the authors write (see our previous Nanowerk Spotlight on this issue: “Pre-coating nanoparticles to better deal with protein coronas“). “More specifically, nanoparticles in contact with biological fluids are quickly surrounded by a layer of proteins that form what is called the protein corona, which has not yet been adequately addressed in the field of cardiac nanotechnology.”
Therefore, to accelerate the clinical translation of nanoparticles and nanostructured materials for use in cardiac nanotechnology, their biological identities must be precisely assessed and reported.

Cell therapy for salvage and regeneration of heart tissue

Over the past decade, the majority of efforts in myocardial regeneration have been centred on cell-based cardiac repair (see for instance: “Nanotechnology based stem cell therapies for damaged heart muscles“).
However, patient-specific therapeutic cells have limitations and nanoparticles could substantially help overcome them by targeting the injured portion of the myocardium.

Delivery of therapeutic molecules to CMs

Nanoparticles demonstrate great potential for delivering therapeutic agents specifically to the ischemic injured heart, although they accumulate mainly at pre-infarcted areas rather than the diseased tissue.
According to the authors, there are two major issues that should be addressed in future studies: 1) as only a low percentage of the injected nanoparticles can pass through the coronary arteries, the targeting capabilities of these particles to the heart tissue should be precisely defined; and 2) the effect of the protein corona on the in vivo release kinetics of the payloads should be characterized. Addressing these critical issues will help scientists design safe and efficient dosage of nanoparticles for biomolecular delivery applications.

Nanostructured scaffolding strategies for myocardial repair

As a bioartificial extracellular matrix (ECM), cardiac tissue scaffolds are engineered to interact optimally with cardiac cells during their gradual degradation and neotissue formation.
A variety of nanobiomaterials have been used to recapitulate the nanoscale features of the native ECM. In comparison with conventional tissue-engineering scaffolds, nanostructured biomaterials (for example, nanofiber/tube and nanoporous scaffolds) offer more biomimetic structural and physiomechanical cues, enhancing protein (molecular) and cellular interactions.
As the field of tissue engineering evolves, more attention is being given to the development of alternative biofabrication strategies to control the nano-scaffold 3D architecture in a more reproducible and patient/tissue-specific manner. Examples include 3D bioprinting and nanoprinting technologies that use computer-assisted layer-by-layer deposition (that is, additive manufacturing) to create 3D structures with sub-micrometer resolution.

Challenges in designing nanoparticles for clinical applications

Despite the enormously large and rapidly growing arsenal of nanoparticle technologies developed to date, few have reached clinical development and even fewer have been approved for clinical use.
This is in part attributed to the challenges associated with controllable and reproducible synthesis of nanoparticles using processes and unit operations that allow for scalable manufacturing required for clinical development and commercialization.
Nanoparticles also encounter unique physiological barriers in the body as compared with small molecule drugs with regard to systemic circulation, access to tissue and intra-cellular trafficking.
The authors point out that, as nanoparticles are increasingly being used in the diagnosis and treatment of cardiac diseases, their potential cardiotoxicity should be examined in detail. Their potential toxicity for cardiac tissue and heart function is of crucial importance for the safety of such nanoparticles.
“To accelerate additional breakthrough discoveries in the field, funding for cardiac nanotechnology should be substantially increased,” the authors conclude their review. “Compared with other biomedical applications of nanotechnology, such as cancer nanotechnology, cardiac nanotechnology has lagged in achieving ‘traction’, and its slower progress also mirrors (at least in part) less investment both from governments/ foundations and financial and strategic investors. During the past few years, however, a growing number of funding opportunities have been created in the field of cardiac nanotechnology, and this has translated into the progress we outline above. We believe that nanomedicines will shift the paradigm of both predictive and therapeutic approaches in cardiac disease in the foreseeable future.”
By Michael Berger Copyright © Nanowerk

HDIAC SOAR Webinar: Uses of Nanotechnology on Surfaces for Military Applications: Video + Presentation


HDIAC Featured_Information_Resources

Homeland Defense & Security Information Analysis Center

 

Click on the Link below to see the Presentation and Notes:

Findings

• Overall
• Nanoceramics
• Metals/metal oxides: silver, copper, titanium dioxide, zinc oxide
• Carbon nanotubes
• Hard surfaces
• Advancements in nanoceramics
• Incorporating superhydrophobic characteristics into surfaces
themselves
• Soft surfaces
• Major advancements in antibacterial coatings
• Developments in smart textiles
• Incorporating nanomaterials into existing fibers/textiles
• Nondurable goods
• Anti-corrosive epoxy coatings with nanomaterials
• Biomedical applications

Homeland Defense & Security Information Analysis Center: PDF Presentation

Materials for (ALL) the Ages ~ Nanomaterials and the (coming) Fourth Industrial Revolution


nano-vacince-28432767823_7110f5293b_oThis nano-vaccine can stimulate an anti-tumour response in patients with cancer. Brenda Melendez and Rita Serda, NIH Image Gallery/Flickr (CC BY-NC 2.0)

HUMAN PROGRESS HAS LONG BEEN DENOTED BY THE DOMINANT MATERIAL OF THE PERIOD. WILL WE SOON BE LIVING IN THE NANOMATERIAL AGE?  

The kind of material used by a society has often served as a yardstick for how developed that society is. From the stone wheel to the iPhone, a bronze axe to a Boeing 747, materials technology has been our constant companion throughout the millennia, and a driving force for continued progress and societal change. Now it is believed that we may be on the cusp of another great materials revolution, this time powered by nanotechnology. With implications for fields ranging from clean energy to medicine, nanotechnology has the potential to have far-reaching impacts on many aspects of our lives, and may earn itself naming rights to the next age in the process.

Sticks and stones and metals

During the Stone Age, our ancestors used natural materials such as animal skins, plant fibres and, of course, stones. These materials were our bread and butter before bread or butter, until humans began to experiment with metalwork. Copper, alloyed with a bit of tin, had such superior properties to stone implements that if a society failed to use the new material, they found themselves in danger of being conquered. Thus, the Bronze Age was born. Bronze had its heyday for millennia, until bronze itself was surpassed by another stronger, more versatile metal.

 

Further advancement in metalwork allowed the production of iron tools and weapons, followed by ones crafted from steel. These implements were stronger and sharper than their bronze counterparts, without a significant increase in weight. There is actually some contention among historians about what constitutes the end of the Iron Age. A common demarcation uses an increase in the survival of written histories, which reduced the burden previously placed on archaeology. However, some believe the Iron Age may have never really ended as iron and steel still play a substantial role in contemporary society.

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 Tools from the Stone age (left) gave way to those required for metal work in the Bronze and Iron ages (above). Patrick Gray/Flickr (CC BY 2.0) and Wikimedia Commons (public domain)

While naming time periods after their defining material has fallen somewhat out of vogue, the progression of society is still driven by advances in materials science and technology.

The industrial revolution, globalization and the Information Age

Coal and the steam engine literally and figuratively fueled the industrial revolution, moulding us into our modern consumer culture. Before the industrial revolution, a high percentage of the population had to farm the land to provide enough food for everyone to survive.

Mechanized farming practices reduced the burden on manpower, while also producing higher yields. As a result, few farmers were required to feed the growing urban populace. This freed up large sections of the population to pursue work in other fields, such as manufacturing, commerce and research. The importance of this transition is still evident today, including our tendency to group countries based on how industrialized they are.

Advances in lightweight materials, such as composites and light metals, facilitated the development of aircraft that fly us around an ever-shrinking globe, and allowed us to be propelled beyond our planet’s life-supporting atmosphere. In the final decades of the 20th century, the world got even smaller following the rapid development of silicon processing chips and personal electronics. The revolutionary impact these silicon products have had on modern society can’t be overstated. Indeed, this article was written, and is likely being read, on devices powered by what is effectively processed sand.

Much to the chagrin of silicon atoms everywhere, we are not currently in the silicon age, but the information or digital age. However, we are likely on the verge of another significant advance in materials technology.

The promises of the nanotechnology age

Scientists have been heralding the Nano Age, proclaiming “nanotechnology will become the most powerful tool the human species has ever used”. This is engineering on an atomic scale, the stuff of science fiction only decades ago. Now, some experts believe nanotechnology will prove to be the foundation of our wildest dreams (or darkest nightmares).
While such claims may seem sensational or outlandish, the inherent potential of nanotechnology is apparent in current research. The University of Queensland (UQ) boasts a nanomaterials research centre with a multidisciplinary team that is working to implement nanomaterials in three key research areas: energy, environment and health. If there can be consensus about issues that are integral to the survival of humanity, the shortlist must surely include these three.

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Read About: Why Everyone Must Get Ready for the Fourth Industrial Revolution

 
Professor Lianzhou Wang is the director of the UQ Nanomaterials Centre, and his work is focused on the first two areas: energy and environment. Prof Wang’s group aims to use nanomaterials to improve the efficiency of solar cells. Due to Australia’s abundant sunshine, the country has a vested interest and solid track record in solar cell research. However, much of that research focuses on improving the efficiency of solar cells, and usually involves increasingly expensive materials and manufacturing techniques. Prof Wang has a more egalitarian approach and is focused on developing renewable energy technology that will be more accessible to the population at large. In his lab, nanomaterials such as metal oxides and quantum dots are used to create cheap, efficient solar cells with the hope of encouraging more widespread utilization of this green power source.

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 Solar panels on rooftops allow residents to take advantage of the Australian sun. Wikimedia Commons (public domain)

 
Using nanotechnology, Prof Wang’s group can make solar cells that are cheaper than currently available commercial silicon and thin film solar cells. They are able to do this because nanomaterials have a much lower processing temperature than conventional materials, which corresponds to a decrease in manufacturing costs. Nanomaterials also impart flexibility during processing and design, as they can be printed on both flexible and rigid substrates.

 
“This is where nanomaterials can play a role: performance, of course, but also cost,” said Prof Wang. By reducing the cost of the solar cells, he hopes to lower the barrier to entry of the market and thereby introduce the technology to a greater proportion of the population. In the case of nanotechnology, it turns out that less really is more.

Solar Shades

 Flexible solar panels have greater utility than their rigid counterparts, and can be used in a wider variety of scenarios, such as on tents. Wikimedia Commons (public domain)

Flexible solar panels have greater utility than their rigid counterparts, and can be used in a wider variety of scenarios, such as on tents. Wikimedia Commons (public domain)
However, not content to call that a good day’s work, Prof Wang is also working toward a solution for another issue plaguing the green energy sector: power storage. Although not particularly nuanced, a common argument against green energies asks what happens when the sun isn’t shining or the wind isn’t blowing. As frustratingly reductive as this may seem, it still presents a serious challenge. The uptake of green energy sources, including solar, is severely limited by inadequate or expensive batteries. The inability to easily and effectively store unused power for a rainy day (pardon the pun) is a limiting factor for many renewable energy technologies.

 
In an effort to address this issue many research groups, including Prof Wang’s, intend to improve batteries with nanotechnology. As with solar cells, the advantage stems from their increased surface area. Nanoparticles, particularly nanocrystallites, have a higher surface area ratio than conventional battery materials, which allows shorter ion diffusion length and faster charge transfer. This not only increases the storage capacity of the battery, but also reduces charging time. Using this technique, Prof Wang’s group believe they have developed new cathode materials for lithium ion batteries that would potentially improve the mileage of electric cars from 450km/charge to 600-700km. “This is an increase of almost a third, and will make these cars competitive with most petrol-powered cars,” said Prof Wang.

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 Electric cars such as the Tesla model S are only as good as their battery life, and nanomaterials have the potential to extend driving time on one charge. Wikimedia Commons (public domain)

 

Exploring how to harness nanomaterials for the betterment of the environment is another key research area for the UQ nanomaterials group. There are a variety of ways nanomaterials can assist in environmental management, but artificial photosynthesis is arguably one of the most innovative. Using nanoparticles as a photoactive catalyst, carbon dioxide in the atmosphere reacts with water to produce by-products including carbon monoxide, methane and hydrogen gas. Prof Wang sums up how remarkable this is: “We can not only remove the CO2 from the atmosphere, we [also] get something useful in the process.” All of the by-products mentioned (carbon monoxide, methane and hydrogen) are potential fuel or power sources. Consequently, artificial photosynthesis not only provides a useful tool for combating climate change, it also generates alternative fuel sources in the process.

Finally, nanotecnology may prove useful for health applications in fields as diverse as targeted drug delivery, gene therapy, diagnostics and tissue engineering, demonstrating its broad potential in medicine. It is thought by some that nanotechnology may hold the key to curing cancer at the genetic level, while also providing insights about immortality.

 

Whether the next great age of humanity is officially labelled the Nano Age or not, nanotechnology will almost certainly play an instrumental role in future innovations and will shape societies for decades to come. Whether it be tackling cancer or climate change, it appears that anything is possible, if we just think small enough.

Tumor Targeting platform with Nanoghosts


By Marcelle Machluf, Associate Professor, The  Faculty of Biotechnology & Food Engineering, Technion – Israel Institute of  Technology, Haifa, Israel.

 

nanomanufacturing-2(Nanowerk Spotlight) The field of drug discovery is  growing at a remarkable pace, leading to the development of many new drugs, most  of which are generally more potent than their predecessors, yet suffer from poor  solubility and/or high toxicities.

Targeted drug-delivery vehicles (e.g.,  liposomes, nano-particles) have often been proposed in an effort to reduce the  side effects of such drugs and improve their overall efficacy for treating  genetic, viral and malignant diseases.   Three main considerations must be addressed when designing any  such delivery system: It should be biocompatible; bioavailable; and highly  selective to its specific target.

Targeting may be improved by conjugating drug carrying vehicles  with targeting moieties that substantially improve their selectivity. For  example, antibodies, proteins etc. have been incorporated into nano-sized  drug-carriers made from polymeric particles, micelles or liposomes, yet their  relatively short circulation time and the complexity of their production render  them too costly and inefficient.

The need for drug delivery vehicles is particularly stressed in  cancer treatment, where high doses of toxic drugs are often required.  Passively-targeted drug-loaded vehicles are still the predominantly used  delivery systems for cancer therapy. Because of their nano-size and physical  properties, such systems were shown to achieve extended circulation times, and  retention in the tumor microenvironment—owing to the Enhanced Permeability and  Retention (EPR) effect of tumor vasculature and microenvironment.

These systems,  nonetheless, are limited by tumor vascularization and permeability that are  largely dependent on the stage of the malignancy and tumor type. Consequently,  active targeting vehicles, once a promising therapeutic approach, have almost  exhausted their potential, particularly in the area of cancer therapy where such  solutions are desperately needed.

In our recent paper (“Reconstructed Stem Cell Nanoghosts: A Natural Tumor  Targeting Platform”) we report on a novel targeted drug-delivery vehicle for  cancer therapy, which can selectively target the tumor niche while delivering an  array of therapeutic agents.   This targeting platform is based on unique vesicles  (‘nanoghosts’) that are produced, for the first time, from intact cell membranes  of stem cells with inherent homing abilities, and which may be loaded with  different therapeutics.

     Binding of nanoghosts to cells Binding of nanoghosts (white arrow) to PC3 cells; cell, green (GFP);  nucleolus, blue (DAPI) evaluated using confocal microscopy over short (3 h)  incubation times. (Reprinted with permission from American Chemical Society)  

We have shown that such vesicles, encompassing the cell surface  molecules and preserving the targeting mechanism of the cells from which they  were made, can outperform conventional delivery systems based on liposomes or  nanoparticles.   These vesicles leverage the benefits related to the size, and  chemical and physical properties of nano-liposomes, allowing them to efficiently  entrap various hydrophilic and hydrophobic drugs, and be administered through  different routes while exhibiting versatile and controllable release profiles.

The prior art pertaining to the design of this unique and novel drug-delivery  platform is drawn from and associated with the production and utilization of  cell-derived vesicles, and the inherent tumor-targeting abilities of mesenchymal  stem cells (MSCs).   A similar therapeutic effect, to what we have achieved, was  previously demonstrated for prostate cancer, using monoclonal antibodies against  N-cadherin, which is highly expressed in castration-resistant prostate cancer;  however, it requires more frequent and higher dosing.

Our therapeutic outcome is comparable to that demonstrated by De  Marra et al. (“New self-assembly nanoparticles and stealth  liposomes for the delivery of zoledronic acid: a comparative study”) who  used no less than three administrations per week of liposomes encapsulating  Zoledronic acid and exceeded the effect achieved by a weekly administration of  an imatinib–mitoxantrone liposomal formulation.

The efficiency of our delivery system is even more compelling in  light of the results reported by Srivastava et al. (“Effects of sequential treatments with chemotherapeutic drugs  followed by TRAIL on prostate cancer in vitro and in vivo”), which  demonstrated no inhibition of tumor growth after two weeks and as many as four  IV administrations of similar quantities of free sTRAIL. The efficacy of our  system also exceeded that of previously reported liposomal formulations  containing sTRAIL tested on glioblastoma and lung cancer.

Till now, nanoghosts made from mammalian cells have been used to  study cell membranes and were utilized for cancer immunotherapy but have never  been tested as targeted drug-delivery vehicles. Recently, we reported a novel  concept describing a targeted drug-delivery system based on nanoghosts, which  were prepared from the outer cell membranes of a non-human cells engineered to  express the human receptor (CCR5) of a viral ligand (gp120) found on the surface  of HIV-infected cells (“Cell derived liposomes expressing CCR5 as a new  targeted drug-delivery system for HIV infected cells”).

Drug-loaded  nanoghosts selectively targeted HIV-infected cells in vitro, achieving  over 60% reduction in their viability compared to empty nanoghosts, free drug,  or nanoghosts applied on control uninfected cells that were not affected at all.   This intrinsically-targeted system, which does not entail the  elaborate production of targeting molecules and their incorporation into passive  vehicles, represents a simpler and more clinically relevant approach than  existing particulate drug-delivery vehicles.

Our success in using nanoghosts to target HIV-infected cells has  prompted us to devise a more sophisticated universal and non-immunogenic  delivery platform, in which the nanoghosts will be produced from stem cells that  are known to naturally target various tumors.   Insights gained from this work may pave the way for new research  utilizing nanoghosts’ inherent targeting to treat not only tumors but also sites  of inflammations, wound healing, and trauma.

The knowledge accumulated on the entrapment of diverse drugs can  facilitate the loading of nanoghosts with nucleic acid (DNA, siRNA etc.) for  gene therapy.   Nanoghosts loaded with MRI contrast agents (Indocyanine or  magnetite nano-crystals) can open unique research avenues in imaging and  diagnosis. Their small size and specific targeting abilities may enable the  nanoghosts to freely travel in the body possibly detecting small and  sub-metastatic cancer nuclei and lesions, which are otherwise undetectable using  conventional methodologies.

Owing to MSCs natural role in regenerative medicine, nanoghosts  can be also investigated in tissue engineering applications for delivering  growth factors for regenerating tissues.   Finally, MSCs can be engineered to express additional targeting  molecules and used to treat other diseases manifested by the expression of  unique targetable ligands.

This work was conducted by PhD students Naama Ester  Toledano-Furman, Yael Lupu-Haber, Limor Kaneti, and the Lab manager Dr. Tomer  Bronshtein.

By Marcelle Machluf, Associate Professor, The  Faculty of Biotechnology & Food Engineering, Technion – Israel Institute of  Technology, Haifa, Israel.

Read more: http://www.nanowerk.com/spotlight/spotid=31548.php#ixzz2apeCNQzx

Nanoparticle Drug Delivery in Cancer Therapy


Published on Mar  3, 2013

http://youtu.be/emEua2eJp1U

 

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Nanobotmodels Company presents vision of modern drug delivery methods using  DNA-origami nanoparticles. In animation you can see cancer therapy using doxorubicin, delivered  by nanomedicine methods.

Nanotechnology Facilitates More Targeted Treatments


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Nanotechnology in Implantable

Medical Devices

 Topics Covered:

Introduction: What is Nanomedicine? Implantable Biosensors      Implantable Glucose Sensors Integration with Monitoring Systems      Chronic Disease Monitoring      Implantable Cardioverter-Defibrillators Implantable Drug Delivery Systems Regulatory Challenges Conclusions Sources

Introduction: What is Nanomedicine?

The term nanomedicine encompasses a broad range of technologies and materials. Types of nanomaterials that have been investigated for use as drugs, drug carriers or other nanomedicinal agents include:

  • Dendrimers
  • Polymers
  • Liposomes
  • Micelles
  • Nanocapsules
  • Nanoparticles
  • Nanoemulsions

Around 250 nanomedicine products are being tested or used in humans, according to a new report that analyzed evolving trends in this sector. According to experts, the long-term impact of nanomedicinal products on human health and the environment is still not certain.

During the last 10 years, there has been steep growth in development of devices that integrate nanomaterials or other nanotechnology. Enhancement of in vivo imaging and testing has been a highly popular area of research, followed by bone substitutes and coatings for implanted devices.

Active and passive cell targeting will continue to be an important focus in nanomedicine. Targeted nano-enhanced solutions have been shown to often enhance existing treatments, and some nanomedicinal techniques are being developed which work as diagnosis and treatment stages simultaneously.

The unknown factor as far as nanotechnology is concerned is whether the increased production, exposure and handling of products and nanomaterials will result in serious impact on the environment and humans. It is possible that toxicity will be the restricting factor for the public acceptance and commercial success of nanotechnology-based products.

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Advances in modern medicine are increasingly relying on electronic devices implanted inside the patient’s body. Nanotechnology allows us to create materials and coatings to construct these devices that are fully biocompatible. Image credit: NASA

Implantable Biosensors

Micro-electromechanical systems (MEMS) and silicon chips that are capable of implantation within the human body may permit interfacing semiconductor devices with living tissues.

Implantable Glucose Sensors

A molecular nanotechnology company Zyvex, specializing in MEMS, chose Diabetech LP as its medical device commercialization and development partner for their wireless sensor implant targeting real-time blood glucose levels in the body. Their novel portable device for patients does not only display the glucose levels from the implant to the patient but also conveys automatically in real time the information to GlucoDynamix, the clinical management system of Diabetech.

Likewise Digital Angel received a patent in October 2006 for their embedded biosensor system. A glucose-sensing RFID microchip is implanted in the patient. The chip can measure glucose levels precisely and can convey the same back to a digital scanner.

This will pave the way for implantable biosensors that can evaluate disease indicators or symptoms and regulate drug release to help in disease treatment.

For example, an implanted glucose sensor can be coupled with an insulin release system and help sufferers of diabetes control their sugar levels without the need for insulin injection or pin-prick tests.

While biocompatibility and long-term stability are being addressed, a number of prototypes have begun to emerge for the management of patients having acute diabetes or to treat epilepsy and other debilitating neurological disorders, and to monitor patients suffering from heart disease.

Integration with Monitoring Systems

Virtual Medical World published an article in November 2005 that stated that a research project financed by the Academy of Finland was underway to develop of minute subcutaneous sensors that can be used for active monitoring of the heart or prosthetic joint function even over long time periods.

For instance, a subcutaneous EKG monitor can detect cardiac arrhythmia, and this data can be wirelessly transmitted to the PC or mobile phone of the physician.

Chronic Disease Monitoring

Guidant is a specialist in treating vascular and cardiac disease and has invested in CardioMEMS based on an article published in Virtual Medical Worlds in November, 2005. CardioMEMS develops novel devices based on MEMS technology to help physicians monitor remotely the progress of chronic diseases like heart failure.

The University of Texas received a grant in 2006 to fund the research and development of an implantable intravascular biosensor that will monitor disease and health progression.

The nano pressure sensor can monitor pressure within the cardiovascular system while the data is transmitted to a wristwatch-like data collection device. The data is transmitted by this external device to a central remote monitoring station where it can be seen by health care providers in real time.

Implantable Cardioverter-Defibrillators

The implantable cardioverter-defibrillator (ICD) has transformed treatment of patients at risk for sudden cardiac death because of ventricular tachyarrhythmias.

The Medtronic CareLink Monitor is a small, convenient device that allows patients to gather information by holding an antenna over the implanted cardiac device. The data is automatically downloaded by the monitor and sent through an internet connection directly to the secure Medtronic CareLink Network. The patient’s data is accessed by clinicians by logging onto a website from any internet-connected computer in their home or office or through the laptop while travelling.

The ICD systems also include portable computer systems that program the implantable cardioverter defibrillators or pacemakers. This interactive system has an LCD touch screen with a user-friendly interface that helps clinicians retrieve and study patient information during routine follow-up visits and easily makes programming changes to the implanted devices.

http://youtu.be/dlert3zh8fo

This video demonstrates how an Implantable Cardioverter Defibrillator or ICD is used to treat dangerously fast or irregular heart beats. Run time: 0:58s.

 

Implantable Drug Delivery Systems

More and more advances in modern medicine are relying on electronic devices implanted inside the patient’s body, to minimize the need for regular examinations, surgery, or in-patient time. Nanotechnology allows us to create materials and coatings to construct these devices that are fully biocompatible, so that they integrate seamlessly with the body’s systems.

Implantable drug delivery systems can deliver small amounts of drugs on a regular basis, so that the patient does not need to be injected. Implantable drug delivery systems give a more consistent drug level in the blood compared to injections, which often makes the treatment more effective and reduces side effects.

By using active monitoring capabilities built into the device, the dosage can be adjusted to suit changes in physical activity, temperature changes and other variables.

In treatments such as chemotherapy, which are usually aimed at a specific area of the body, the device can be implanted near the target area, keeping drug concentration much lower in the rest of the body.

Smart implantable insulin pumps are designed so as to offer relief for people with Type I diabetes. These are implantable, active drug delivery devices that build on and go beyond the capabilities offered by passive glucose biosensors.

Regulatory Challenges

Nanomaterials and nanotechnology offer significant promise in the medical device community, as well as many other industry sectors. They also pose a number of regulatory challenges, which as time goes by will become more pressing than the technical challenges. Some of the difficulaties in regulating nanomedical devices are as follows:

  • It is important to determine the intended use of the product, but it can be difficult to define uses among several stakeholders.
  • The indicated patient population must be understood, and there should be clarity about the claimed benefits of a product.
  • Throughout the submission process of products for market approval, it is important to communicate with the FDA or other relevant authority. Manufacturing processes are highly critical for a successful submission. Marketing, sales, labeling and international issues, training and education are all part of this effort.

Conclusions

Nanomedicine will transform healthcare in the coming years, changing the day-to-day business practices of health care organizations and improving how patient care is provided.

Health care organizations must monitor innovations continually, perform clinical trials and developments related to this area and also other evolving health IT solutions.

There is a lot of research going on in this area; however not many products have reached the commercialization stage. There is still a long way to go before all these promising devices become a part of our daily lives.

Sources

Nanotechnology’s Revolutionary Next Phase: Eric Drexler on “APM”


QDOTS imagesCAKXSY1K 8The term “nanotechnology” has been bandied about so much over the last few decades that even the researcher who popularized the term is the first to point out that it’s lost its original meaning. Nanotech, or the manipulation of matter on atomic and molecular scales, is currently used to describe micro-scale technology in everything from space technology to biotech.

 

As such, nanotech has already changed the world. But the fruition of atomically precise manufacturing (APM) — nanotech’s next phase — promises to create such “radical abundance” that it will not only change industry but civilization itself.

At least that’s the view of Eric Drexler, considered by most to be the father of nanotechnology. An American engineer, technologist and author with three degrees from M.I.T., Drexler is currently at the “Programme on the Impacts of Future Technology” at Oxford University in the U.K.

Forbes.com questioned Drexler about points discussed in his forthcoming book, Radical Abundance: How a Revolution in Nanotechnology Will Change Civilization, due out in May.

Has nanotechnology, as most of the world currently understands it, been over-hyped? At the outset, “nanotechnology” essentially meant atomically precise manufacturing (APM). But by the time something called nanotechnology won large-scale funding a decade ago, the term sometimes meant APM, and sometimes meant something more like conventional materials science. But expecting to get APM-level technologies out of typical areas of materials science is like expecting to get a Swiss watch out of a cement mixer. [APM] progress has been in the molecular sciences. People looking to materials science for progress in APM have been setting themselves up to be blindsided, because some of the most important boostrapping technologies for APM are not labeled “nanotechnology.”

In “Radical Abundance,” you note that APM-level production technology will allow a box on a desktop “to manufacture an infinite range of products drawn from a digital library.” This almost sounds like magic. How would the atoms be arranged and manipulated to facilitate the manufacturing process?

An ordinary printer shows how digital information can be used to arrange small things — pixels — to make a virtually infinite range of images. By doing something similar with small bits of matter, and APM-level technologies can fabricate a virtually infinite range of products. 3D printing also illustrates this principle.

Carbon NanotubeImagine factory machinery putting small components together to make larger components and you have a good idea of how APM-based production can work. Down at the bottom, the parts are simple molecules from ordinary commercial materials in a can or a drum, somewhat like large ink cartridges. Simple molecules are atomically precise, so they make a good starting point for atomically precise manufacturing. This works if the factory machines themselves are atomically precise and guide molecular motions accurately enough, and physics shows that nanoscale machines can, in fact, do this.

Factories that use very small machines can be very compact, just a few times larger than what they produce. A desktop-scale machine could manufacture a tablet computer or a roll of solar photovoltaic cells.

What about the cost-effectiveness of APM? Cost-effectiveness depends on both production cost and product value. APM products can have very high performance and value because atomically precise materials based on carbon nanotubes can be extremely strong and lightweight, because atomically precise computer devices can far outperform today’s nanoscale electronics, and so on through a range of other examples.

Production costs can be low because the raw materials are inexpensive and the processing can go straight from raw materials to final products using highly productive machinery. The key insight here is that nanoscale mechanical devices can move and act almost exactly like larger machines, but moving at much higher frequencies. This is a consequence of physical scaling laws of the kind that [physicist] Richard Feynman described almost 50 years ago, and it enables high throughput. So the prospect is a technology that combines high performance with low cost, typically by large factors.

To be an exploratory engineer means applying conservative engineering principles — margins of safety, redundant options, and so on — and design analysis based on well-established, textbook-quality scientific knowledge. This is the only way to draw reliable conclusions about what can be accomplished.

The place to look for new and surprising results is in the range of technologies that are beyond reach of current fabrication technologies. APM-level technologies are in this range. We can see paths forward toward these technologies — using today’s molecular tools to step by step build better tools. But a clear view isn’t the same as a short path. APM-level technologies are not around the corner.

Would APM make revolutionary inroads into biotech — specifically, in developing nano-machines that could unclog arteries; reverse brain damage in stroke victims; or even manufacture a truly robust artificial heart? APM is very different from biotechnology (think of the difference between a car and a horse). But we already see nanoscale atomically precise devices being used to read and synthesize DNA, devices borrowed from biological molecular machinery. Nanoscale atomically precise technologies like these can be made much faster and more efficient. Nanomedicine is already researching nanoscale functional particles that can circulate in the body and target cancer cells. Technologies of this kind have enormous room for improvement, and advances in atomically precise fabrication will be the key. The body relies on atomically precise devices to do its work, and atomically precise devices are the best way to accomplish precise medical interventions at the molecular level.

Would APM lower the cost of access to outer space? The main barrier to space activity today is cost. With the ability to make materials tens of times stronger and lighter than aluminum, and at a low cost per kilogram, access to space becomes far more practical. The difficulties of producing high-performance, low-defect, high-reliability systems also decline sharply with atomically precise manufacturing.

In what fields would APM cause the most pronounced economic disruption and the collapse of global supply chains to more local chains? The digital revolution had far-reaching effects on information industries. APM-based production promises to have similarly far-reaching effects, but transposed into the world of physical products. In thinking about implications for international trade and economic organization, three aspects should be kept in mind: a shift from scarce to common raw materials, a shift from long supply chains to more direct paths from raw materials to finished products, and a shift toward flexible, localized manufacturing based on production systems with capabilities that are comparable on-demand printing. This is enough to at least suggest the scope of the changes to expect from a mature form of APM-based production — which again is a clear prospect but emphatically not around the corner.

Would APM help make war obsolete? I don’t see that anything will make war obsolete, but the prospect of APM-level technologies changes national interests in two major ways:

By deeply reducing the demand for scarce resources — including petroleum — APM technologies will reduce the motivations for geopolitical struggles for what are now considered strategic resources.

Secondly, by making calculations of future military power radically uncertain, the prospect of these technologies gives good reason to examine approaches to cooperative development merged with confidence-building mutual transparency among major powers. Changes in national interests will call for developing [military] contingency plans premised on the emergence of these technologies.

A Steel worker is pictured as he works with mo...Atomically Precise Manufacturing would make steel works such as this one obsolete. (Image Credit: AFP/Getty Images via @daylife)

When will we actually see the onset of the APM revolution? The paths forward require further advances in atomically precise fabrication, an area that began with organic chemistry more than a century ago and continues to make great strides. A sharper engineering focus will bring faster progress and further rewards, just as progress in atomically precise fabrication has brought rewards since the beginning in science, industry, and medicine.

Although advanced objectives like full-scale APM stand beyond a normal business R&D investment horizon, incremental steps in key technologies are steadily emerging. But we need a more focused program of design, analysis, research, and development.

Do all roads lead to APM? Thus, is some form of APM likely to be ubiquitous among intelligent civilizations in the galaxy, if of course such civilizations exist? There’s no substitute for atomic precision because there’s no substitute for precisely controlling the structure of matter. The only known way to do this is by guiding the motion of molecules to put them in place, according to plan, by means of directed bonding — in other words, by some form of atomically precise manufacturing. Since there are many ways to develop these technologies, I’d say that all roads forward do indeed lead to APM.