How To Track Blood Flow In Tiny Vessels

Scientists have designed gold nanoparticles, no bigger than 100 nanometres, which can be coated and used to track blood flow in the smallest blood vessels in the body. By improving our understanding of blood flow in vivo the nanoprobes represent an opportunity to help in the early diagnosis of diseaseLight microscopy is a rapidly evolving field for understanding in vivo systems where high resolution is required. It is particularly crucial for cardiovascular research, where clinical studies are based on ultrasound technologies which inherently have lower resolution and provide limited information.

The ability to monitor blood flow in the sophisticated vascular tree (notably in the smallest elements of the microvasculaturecapillaries) can provide invaluable information to understand disease processes such as thrombosis and vascular inflammation. There are further applications for the improved delivery of therapeutics, such as targeting tumours.

Currently, blood flow in the microvasculature is poorly understood. Nanoscience is uniquely placed to help understand the processes happening in the micron-dimensioned vessels. Designing probes to monitor blood flow is challenging because of the environment; the high protein levels in plasma and the high red blood cell concentrations are detrimental to optical imaging. Conventional techniques rely on staining red blood cells, using organic dyes with short-lived usage due to photobleaching, as the tracking motif. The relatively large size of the red blood cells (7-8 micrometres), which are effectively the probes, limits the resolution in imaging and analysis of flow dynamics of the smallest vessels which are of a similar width. Therefore, to have more detailed resolution and information about the blood flow in the microvasculature, even smaller probes are required.

The key to these iridium-coated nanoparticles lies in both their small size, and in the characteristic luminescent properties. The iridium gives a luminescent signal in the visible spectrum, providing an optical window which can be detected in blood. It is also long-lived compared to organic fluorophores, while the tiny gold particles are shown to be ideal for tracking flow and detect clearly in tissues“, explains Professor Zoe Pikramenou, from the School of Chemistry at  the University of Birmingham.

The findings have been published in the journal Nanomedicine.


How To Fix Duchenne Muscular Dystrophy

Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.

Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.

CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.

In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.

CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.

The study was published in the journal Nature Biomedical Engineering.


Paper Supercapacitor

By coating ordinary paper with layers of gold nanoparticles and other materials, researchers have fabricated flexible paper supercapacitors that exhibit the best performance of any textile-type supercapacitor to date. In particular, the paper supercapacitors address one of the biggest challenges in this area, which is to achieve a high energy density in addition to an already high power density, since both properties are essential for realizing high-performance energy-storage devices. In the future, flexible paper supercapacitors could be used in wearable electronics for biomedical, consumer, and military applications. The researchers, led by Seung Woo Lee at the Georgia Institute of Technology and Jinhan Cho at Korea University, have published a paper on the flexible paper supercapacitor electrodes in a recent issue of Nature Communications. As energy-storage devices, supercapacitors have several advantages over batteries, such as a higher power density, rapid charge/discharge rate, and longer lifetime, yet they lag behind batteries in energy density (the amount of energy that can be stored in a given amount of space). Although several methods have been attempted to improve the energy density of paper supercapacitors by coating them with various conductive materials, often these methods have the drawback of reducing the power density.

The paper electrodes based on layer-by-layer-assembled metal nanoparticles exhibit metal-like electric conductivity, paper-like mechanical properties, and a large surface area without any thermal treatment and/or mechanical pressing,” explains coauthor Yongmin Ko at Korea University. “The periodic insertion of metal nanoparticles within high-energy nanoparticle-based paper electrodes could resolve the critical tradeoff in which an increase in the loading amount of materials to enhance the energy density of supercapacitors decreases the power density.”
Tests  showed that the flexible paper supercapacitors had a maximum capacitance that is higher than any previously reported textile-based supercapacitor. In addition, the new devices exhibits an excellent capacity retention, demonstrated by a 90% capacity retention after 5,000 bending cycles.


Blood Cells Deliver Drugs To Kill Cancer

For the first time, WSU researchers have demonstrated a way to deliver a drug to a tumor by attaching it to a blood cell. The innovation could let doctors target tumors with anticancer drugs that might otherwise damage healthy tissues.

To develop the treatment, a team led by Zhenjia Wang, an assistant professor of pharmaceutical sciences, worked at the microscopic scale using a nanotherapeutic particle so small that 1,000 of them would fit across the width of a hair. By attaching a nanoscale particle to an infection-fighting white blood cell, the team showed they can get a drug past the armor of blood vessels that typically shield a tumor. This has been a major challenge in nanotechnology drug delivery.

Working with colleagues in Spokane and China, Wang implanted a tumor on the flank of a mouse commonly chosen as a model for human diseases. The tumor was exposed to near-infrared light, causing an inflammation that released proteins to attract white blood cells, called neutrophils, into the tumor. The researchers then injected the mouse with gold nanoparticles treated with antibodies that mediate the union of the nanoparticles and neutrophils. When the tumor was exposed to infrared light, the light’s interaction with the gold nanoparticles produced heat that killed the tumor cells, Wang said. In the future, therapists could attach an anticancer drug like doxorubicin to the nanoparticle. This could let them deliver the drug directly to the tumor and avoid damaging nearby tissues, Wang said.

We have developed a new approach to deliver therapeutics into tumors using the white blood cells of our body,” Wang said. “This will be applied to deliver many anticancer drugs, such as doxorubicin, and we hope that it could increase the efficacy of cancer therapies compared to other delivery systems.”

Wang and Chu’s colleagues on the research are postdoctoral researcher Dafeng Chu, Ph.D. student Xinyue Dong, Jingkai Gu of Jilin University and Jingkai Gu of the University of Macau.

The researchers reported on the technique in the latest issue of the journal Advanced Materials.


Nanoparticles From Air Pollution Travel Into Blood To Cause Heart Disease

Inhaled nanoparticles – like those released from vehicle exhausts – can work their way through the lungs and into the bloodstream, potentially raising the risk of heart attack and stroke, according to new research part-funded by the British Heart Foundation. The findings, published today in the journal ACS Nano, build on previous studies that have found tiny particles in air pollution are associated with an increased risk of cardiovascular disease, although the cause remains unproven. However, this research shows for the first time that inhaled nanoparticles can gain access to the blood in healthy individuals and people at risk of stroke. Most worryingly, these nanoparticles tend to build-up in diseased blood vessels where they could worsen coronary heart disease – the cause of a heart attack.

It is not currently possible to measure environmental nanoparticles in the blood. So, researchers from the University of Edinburgh, and the National Institute for Public Health and the Environment in the Netherlands, used a variety of specialist techniques to track the fate of harmless gold nanoparticles breathed in by volunteers. They were able to show that these nanoparticles can migrate from the lungs and into the bloodstream within 24 hours after exposure and were still detectable in the blood three months later. By looking at surgically removed plaques from people at high risk of stroke they were also able to find that the nanoparticles accumulated in the fatty plaques that grow inside blood vessels and cause heart attacks and strokesCardiovascular disease (CVD) – the main forms of which are coronary heart disease and stroke – accounts for 80% of all premature deaths from air pollution.


It is striking that particles in the air we breathe can get into our blood where they can be carried to different organs of the body. Only a very small proportion of inhaled particles will do this, however, if reactive particles like those in air pollution then reach susceptible areas of the body then even this small number of particles might have serious consequences,”  said Dr Mark Miller, Senior Research Fellow at the University of Edinburgh who led the study.


Japan Bets On Hydrogen As A Green Energy Source

Hydrogen gas is a promising alternative energy source to overcome our reliance on carbon-based fuels, and has the benefit of producing only water when it is reacted with oxygen. However, hydrogen is highly reactive and flammable, so it requires careful handling and storage. Typical hydrogen storage materials are limited by factors like water sensitivity, risk of explosion, difficulty of control of hydrogen-generation.

alstom-hydrogen-electric-train Hydrogen gas can be produced efficiently from organosilanes, some of which are suitably air-stable, non-toxic, and cheap. Catalysts that can efficiently produce hydrogen from organosilanes are therefore desired with the ultimate goal of realizing safe, inexpensive hydrogen production in high yield. Ideally, the catalyst should also operate at room temperature under aerobic conditions without the need for additional energy input. A research team led by Kiyotomi Kaneda and Takato Mitsudome at Osaka University have now developed a catalyst that realizes efficient environmentally friendly hydrogen production from organosilanes. The catalyst is composed of gold nanoparticles with a diameter of around 2 nm supported on hydroxyapatite.

The team then added the nanoparticle catalyst to solutions of different organosilanes to measure its ability to induce hydrogen production. The nanoparticle catalyst displayed the highest turnover frequency and number attained to date for hydrogen production catalysts from organosilanes. For example, the  converted 99% of dimethylphenylsilane to the corresponding silanol in just 9 min at room temperature, releasing an equimolar amount of hydrogen gas at the same time. Importantly, the catalyst was recyclable without loss of activity. On/off switching of hydrogen production was achieved using the nanoparticle catalyst because it could be easily separated from its organosilane substrate by filtration. The activity of the catalyst increased as the nanoparticle size decreased.

A prototype portable hydrogen fuel cell containing the nanoparticle catalyst and an organosilane substrate was fabricated. The fuel cell generated power in air at room temperature and could be switched on and off as desired.

Generation of hydrogen from inexpensive organosilane substrates under ambient conditions without additional energy input represents an exciting advance towards the goal of using hydrogen as a green energy source.


Nanoparticles Eradicate PreCancerous Cells In The Liver

According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri (MU) – School of Medicine  researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and invitro human cells.

liver cancer

The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites,” said Kattesh Katti, PhD, Curators’ Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. “For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants.”

The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy.

Gum Arabic is a natural gum made of the hardened sap from acacia trees,” said Katti, who also serves as director of the MU Institute of Green Nanotechnology and Professor of Medical Research at the MU School of Medicine. “It is FDA-approved for human consumption and is primarily used in the food industry as an additive. It also promotes adhesion of gold nanoparticles engineered to attract to precancerous and malignant cells – which are much more susceptible to lower levels of heat than healthy cells. Once the nanoparticles travel and adhere to cancerous cells, they are heated to a temperature that destroys them but leaves healthy tissue unaffected.”

Katti’s team studied a total of 224 mice. Half were identified as having precancerous cells in their livers. The other half had normal liver tissue. Outside of the control group, the mice received either an intravenous injection of gum Arabic alone or gum Arabic-encapsulated gold nanoparticles with or without laser therapy.

The administration of gum Arabic, gold nanoparticles and photothermal therapy caused no change to healthy tissue, which confirmed the safe use of these treatments,” Katti said. “However, the use of gum Arabic-encapsulated nanoparticles combined with photothermal therapy resulted in the targeted eradication of the precancerous cells and their genetic code in both our mice model and the human invitro cell model we developed for this study.”


Gold Nanoparticles Fight Pancreatic Cancer

A diagnosis of pancreatic cancer is often a death sentence because chemotherapy and radiation have little impact on the disease. In the U.S. this year, some 53,000 new cases will be diagnosed, and 42,000 patients will die of the disease, according to the National Institute of Health. But research now being reported in ACS Nano could eventually lead to a new type of treatment based on gold nanoparticles.

pancreas2Pancreatic cancer is an aggressive, often fatal condition, but researchers are looking to gold nanoparticles to develop new treatments

Scientists from the University of Oklahoma Health Sciences Center (OUHCS) have previously studied these tiny gold particles as a vehicle to carry chemotherapy drug molecules into tumors or as a target to enhance the impact of radiation on tumors. In addition, Priyabrata Mukherjee and colleagues previously found that gold nanoparticles themselves could limit tumor growth and metastasis in a model of ovarian cancer in mice.

Now, the team has determined that the same holds true for mouse models of pancreatic cancer. But interestingly, the new work revealed details about cellular communication in the area surrounding pancreatic tumors. By interrupting this communication — which is partly responsible for this cancer’s lethal nature — the particles reduced the cell proliferation and migration that ordinarily occurs near these tumors. Gold nanoparticles of the size used in the new study are not toxic to normal cells, the researchers note.


Tiny Diamonds Revolutionize Nanotechnology

Nanomaterials have the potential to improve many next-generation technologies. They promise to speed up computer chips, increase the resolution of medical imaging devices and make electronics more energy efficient. But imbuing nanomaterials with the right properties can be time consuming and costly. A new, quick and inexpensive method for constructing diamond-based hybrid nanomaterials in bulk could launch the field from research to applications. University of Maryland (UMD) researchers developed a method to build diamond-based hybrid nanoparticles in large quantities from the ground up, thereby circumventing many of the problems with current methods.

The process begins with tiny, nanoscale diamonds that contain a specific type of impurity: a single nitrogen atom where a carbon atom should be, with an empty space right next to it, resulting from a second missing carbon atom. This “nitrogen vacancyimpurity gives each diamond special optical and electromagnetic properties. By attaching other materials to the diamond grains, such as metal particles or semiconducting materials known as “quantum dots,” the researchers can create a variety of customizable hybrid nanoparticles, including nanoscale semiconductors and magnets with precisely tailored properties.


If you pair one of these diamonds with silver or gold nanoparticles, the metal can enhance the nanodiamond’s optical properties. If you couple the nanodiamond to a semiconducting quantum dot, the hybrid particle can transfer energy more efficiently,” said Min Ouyang, an associate professor of physics at UMD and senior author on the study.

The technique is described in the June 8 issue of the journal Nature Communications.


Nano Biosensor Detects Rapidly Flu Virus At Low Cost

The Department of Applied Physics (AP) and Interdisciplinary Division of Biomedical Engineering (BME) of The Hong Kong Polytechnic University (PolyU) have jointly developed a novel nano biosensor for rapid detection of flu and other viruses. PolyU‘s new invention utilizes an optical method called upconversion luminescence resonance energy transfer (LRET) process for ultrasensitive virus detection. It involves simple operational procedures, significantly reducing its testing duration from around 1-3 days to 2-3 hours, making it more than 10 times quicker than traditional clinical methods. Its cost is around HK$20 per sample, which is 80% lower than traditional testing methods. The technology can be widely used for the detection of different types of viruses, shedding new light on the development of low-cost, rapid and ultrasensitive detection of different viruses.

flu virusTraditional biological methods for flu virus detection include genetic analysis — reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) used in immunology. However, RT-PCR is expensive and time-consuming while the sensitivity for ELISA is relatively low. Such limitations make them difficult for clinical use as a front-line and on-site diagnostic tool for virus detection, paving the way for PolyU‘s development of the new upconversion nanoparticle biosensor which utilizes luminescent technique in virus detection.

PolyU‘s researchers have developed a biosensor based on luminescent technique which operates like two matching pieces of magnet with attraction force. It involves the development of upconversion nanoparticles (UCNPs) conjugated with a probe oligo whose DNA base pairs are complementary with that of the gold nanoparticles (AuNPs) flu virus oligo.

The related results have been recently published in ACS Nano and Small, specialized journals in nano material research.


Electronic Circuits Mimic The Human Brain

Researchers of the MESA+ Institute for Nanotechnology and the CTIT Institute for ICT Research at the University of Twente in The Netherlands have demonstrated working electronic circuits that have been produced in a radically new way, using methods that resemble Darwinian evolution. The size of these circuits is comparable to the size of their conventional counterparts, but they are much closer to natural networks like the human brain. The findings promise a new generation of powerful, energy-efficient electronics, and have been published in the journal Nature Nanotechnology. The approach of the researchers at the University of Twente is based on methods that resemble those found in Nature. They have used networks of gold nanoparticles for the execution of essential computational tasks. Contrary to conventional electronics, they have moved away from designed circuits. By using ‘designless‘ systems, costly design mistakes are avoided. The computational power of their networks is enabled by applying artificial evolution. This evolution takes less than an hour, rather than millions of years. By applying electrical signals, one and the same network can be configured into 16 different logical gates. The evolutionary approach works around – or can even take advantage of – possible material defects that can be fatal in conventional electronics.

One of the greatest successes of the 20th century has been the development of digital computers. During the last decades these computers have become more and more powerful by integrating ever smaller components on silicon chips. However, it is becoming increasingly hard and extremely expensive to continue this miniaturisation. Current transistors consist of only a handful of atoms. It is a major challenge to produce chips in which the millions of transistors have the same characteristics, and thus to make the chips operate properly. Another drawback is that their energy consumption is reaching unacceptable levels. It is obvious that one has to look for alternative directions, and it is interesting to see what we can learn from nature. Natural evolution has led to powerful ‘computers’ like the human brain, which can solve complex problems in an energy-efficient way. Nature exploits complex networks that can execute many tasks in parallel.


Gold Nanotubes Attack Cancer Cells

Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells.
Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said: “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects. Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

gold nanotubes
Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it”, said the Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds and who is the study’s corresponding author. When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

The study, published in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer.