TAG: "Nanotechnology"

Scientists develop new nanoscale method to fight cancer


Nanovalves have special molecules that respond to energy from two-photon light exposure.

Jeffrey Zink, UCLA

Researchers from UCLA’s Jonsson Comprehensive Cancer Center have developed an innovative cancer-fighting technique in which custom-designed nanoparticles carry chemotherapy drugs directly to tumor cells and release their cargo when triggered by a two-photon laser in the infrared red wavelength.

The research findings by UCLA’s Jeffrey Zink, a professor of chemistry and biochemistry, and Fuyu Tamanoi, a professor of microbiology, immunology and molecular genetics, and their colleagues were published online Feb. 20 in the journal Small and will appear in a later print edition.

Light-activated drug delivery holds promise for treating cancer because it give doctors control over precisely when and where in the body drugs are released. Delivering and releasing chemotherapy drugs so that they hit only tumor cells and not surrounding healthy tissues can greatly reduce treatment side effects and increase the drugs’ cancer-killing effect. But the development of a drug-delivery system that responds to tissue-penetrating light has been a major challenge.

To address this, the teams of Tamanoi and Zink, which included scientists from the Jonsson Cancer Center’s cancer nanotechnology and signal transduction and therapeutics programs, collaborated with Jean-Olivier Durand from France’s University of Montpellier to develop a new type of nanoparticle that can absorb energy from tissue-penetrating light.

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How nanotechnology can help fight cancer


UCLA researcher highlights advances.

Dean Ho, UCLA

Dean Ho, UCLA

As cancer maintains its standing as the second leading cause of death in the U.S., researchers have continued their quest for safer and more effective treatments. Among the most promising advances has been the rise of nanomedicine, the application of tiny materials and devices whose sizes are measured in the billionths of a meter to detect, diagnose and treat disease.

A new research review co-authored by a UCLA professor provides one of the most comprehensive assessments to date of research on nanomedicine-based approaches to treating cancer and offers insight into how researchers can best position nanomedicine-based cancer treatments for FDA approval.

The article, by Dean Ho, professor of oral biology and medicine at the UCLA School of Dentistry, and Edward Chow, assistant professor at the Cancer Science Institute of Singapore and the National University of Singapore, was published online by the peer-reviewed journal Science Translational Medicine. Ho and Chow describe the paths that nanotechnology-enabled therapies could take — and the regulatory and funding obstacles they could encounter — as they progress through safety and efficacy studies.

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Nanosponge vaccine fights MRSA toxins


Approach could be used to create vaccines that protect against a wide range of toxins.

The glowing yellow specks in the image show uptake of the nanosponge vaccine by a mouse dendritic cell, which is an immune-system cell.

The glowing yellow specks in the image show uptake of the nanosponge vaccine by a mouse dendritic cell, which is an immune-system cell.

Nanosponges that soak up a dangerous pore-forming toxin produced by MRSA (methicillin-resistant Staphylococcus aureus) could serve as a safe and effective vaccine against this toxin. This “nanosponge vaccine” enabled the immune systems of mice to block the adverse effects of the alpha-haemolysin toxin from MRSA — both within the bloodstream and on the skin. Nanoengineers from UC San Diego described the safety and efficacy of this nanosponge vaccine in the Dec. 1 issue of Nature Nanotechnology.

The nanosponges at the foundation of the experimental “toxoid vaccine” platform are bio-compatible particles made of a polymer core wrapped in a red-blood-cell membrane. Each nanosponge’s red-blood-cell membrane seizes and detains the Staphylococcus aureus (staph) toxin alpha-haemolysin without compromising the toxin’s structural integrity through heating or chemical processing. These toxin-studded nanosponges served as vaccines capable of triggering neutralizing antibodies and fighting off otherwise lethal doses of the toxin in mice.

Toxoid vaccines protect against a toxin or set of toxins, rather than the organism that produces the toxin(s). As the problem of antibiotic resistance worsens, toxoid vaccines offer a promising approach to fight infections without reliance on antibiotics.

Liangfang Zhang, UC San Diego

Liangfang Zhang, UC San Diego

“With our toxoid vaccine, we don’t have to worry about antibiotic resistance. We directly target the alpha-haemolysin toxin,” said Liangfang Zhang, a nanoengineering professor at UC San Diego Jacobs School of Engineering and the senior author on the paper. Targeting the alpha-haemolysin toxin directly has another perk. “These toxins create a toxic environment that serves as a defense mechanism which makes it harder for the immune system to fight Staph bacteria,” explained Zhang.

Beyond MRSA and other staph infections, the nanosponge vaccine approach could be used to create vaccines that protect against a wide range of toxins, including those produced by E. coli and H. pylori.

This work from Zhang’s Nanomaterials and Nanomedicine Laboratory at the UC San Diego included nanoengineering post-doctoral researcher Che-Ming “Jack” Hu, nanoengineering graduate student Ronnie Fang, and bioengineering graduate student Brian Luk.

The researchers found that their nanosponge vaccine was safe and more effective than toxoid vaccines made from heat-treated staph toxin. After one injection, just 10 percent of staph-infected mice treated with the heated version survived, compared to 50 percent for those who received the nanosponge vaccine. With two more booster shots, survival rates with the nanosponge vaccine were up to 100 percent, compared to 90 percent with the heat-treated toxin.

“The nanosponge vaccine was also able to completely prevent the toxin’s damages in the skin, where MRSA infections frequently take place,” said Zhang, who is also affiliated with the Moores Cancer Center at UC San Diego.

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Discovery could increase survival in sepsis


UC Santa Barbara findings have potential to translate into millions of saved lives.

Jamey Marth, UC Santa Barbara

Jamey Marth, UC Santa Barbara

Sepsis, the body’s response to severe infections, kills more people than breast cancer, prostate cancer and HIV/AIDS combined. On average, 30 percent of those diagnosed with sepsis die.

A study conducted by Jamey Marth, director of UC Santa Barbara’s Center for Nanomedicine and professor of the Sanford-Burnham Medical Research Institute, reports a new method to increase survival in sepsis. The results appear today in the Proceedings of the National Academy of Science.

Building on earlier work in which Marth’s team revealed the biological purpose of the Ashwell-Morell receptor (AMR) in the liver, the new discovery not only describes the AMR’s protective mechanism, but also outlines a way to leverage it for therapeutic use. Sepsis often triggers widespread blood coagulation and thrombosis, which can lead to organ failure and death.

The researchers found that the AMR protects the host by the rapid removal of the prothrombotic components normally present in the bloodstream, including platelets and specific coagulation factors that contribute to the formation of blood clots. The study elucidates this mechanism of AMR function in mitigating the lethal effects of excessive blood coagulation and thrombosis in sepsis.

The key is neuraminidase, an enzyme that is present in many pathogenic microorganisms, such as Streptococcus pneumoniae, the bacteria used in this study, which remains one of the top five causes of death worldwide. Pathogens use neuraminidase to get into cells, but once the pathogen enters the bloodstream, the enzyme then remodels the surface of platelets and other glycoproteins in circulation. This remodeling signals the AMR to remove those platelets and coagulation factors before they have a chance to contribute to the lethal coagulopathy of sepsis.

“It’s a highly conserved protective mechanism never before identified,” said Marth, who is also Carbon Professor of Biochemistry and Molecular Biology and Mellichamp Professor of Systems Biology at UCSB. “The host has evolved this protective mechanism over millions of years as a way to compensate for the lethal impact of the pathogen on our coagulation system.”

The scientists wondered what would happen if they could pre-activate and augment AMR function in the early phases of sepsis. To answer that question, they infected mice with Streptococcus pneumoniae and then gave them a single dose of neuraminidase. “We were able to increase survival twofold,” said Marth. “It’s remarkable, and because we see the same mechanism active in human sepsis there is excitement by the potential of this approach to save millions of lives.”

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Researchers’ two-step method shows promise in fighting pancreatic cancer


Techniques uses two types of nanoparticles.

Andre Nel, UCLA

Andre Nel, UCLA

Researchers at UCLA’s Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer that uses two different types of nanoparticles, the first type clearing a path into tumor cells for the second, which delivers chemotherapy drugs.

The research team, led by Dr. Andre Nel, a UCLA professor of nanomedicine and a member of the California NanoSystems Institute at UCLA, and Dr. Huan Meng, a UCLA adjunct assistant professor of nanomedicine, has shown that this new drug-delivery technique is effective in treating pancreatic cancer in a mouse model.

The results of the study are published online in the journal ACS Nano and will be featured in the November 2013 print issue.

Pancreatic ductal adenocarcinoma, or pancreatic cancer, is a deadly disease that is nearly impossible to detect until it is in the advanced stage. Treatment options are limited and have low success rates. The need for innovative and improved treatment of pancreatic cancer cannot be overstated, the researchers said, as a pancreatic cancer diagnosis has often been synonymous with a death sentence.

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The future of dental implants?


Nanodiamonds could be used to improve bone growth, prevent dental implant failure.

NanodiamondsUCLA researchers have discovered that diamonds on a much, much smaller scale than those used in jewelry could be used to promote bone growth and the durability of dental implants.

Nanodiamonds, which are created as byproducts of conventional mining and refining operations, are approximately four to five nanometers in diameter and are shaped like tiny soccer balls.

Scientists from the UCLA School of Dentistry, the UCLA Department of Bioengineering and Northwestern University, along with collaborators at the NanoCarbon Research Institute in Japan, may have found a way to use them to improve bone growth and combat osteonecrosis, a potentially debilitating disease in which bones break down due to reduced blood flow.

When osteonecrosis affects the jaw, it can prevent people from eating and speaking; when it occurs near joints, it can restrict or preclude movement. Bone loss also occurs next to implants such as prosthetic joints or teeth, which leads to the implants becoming loose — or failing.

Implant failures necessitate additional procedures, which can be painful and expensive, and can jeopardize the function the patient had gained with an implant. These challenges are exacerbated when the disease occurs in the mouth, where there is a limited supply of local bone that can be used to secure the prosthetic tooth, a key consideration for both functional and aesthetic reasons.

The study, led by Dr. Dean Ho, professor of oral biology and medicine and co-director of the Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the UCLA School of Dentistry, appears online in the peer-reviewed Journal of Dental Research.

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Smartphone ‘microscope’ can detect a single virus, nanoparticles


Device created by UCLA researchers weighs less than half a pound.

OzcanNanoCamera

OzcanNanoCamera

Your smartphone now can see what the naked eye cannot: A single virus and bits of material less than one-thousandth of the width of a human hair.

Aydogan Ozcan, a professor of electrical engineering and bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, and his team have created a portable smartphone attachment that can be used to perform sophisticated field testing to detect viruses and bacteria without the need for bulky and expensive microscopes and lab equipment. The device weighs less than half a pound.

“This cellphone-based imaging platform could be used for specific and sensitive detection of sub-wavelength objects, including bacteria and viruses and therefore could enable the practice of nanotechnology and biomedical testing in field settings and even in remote and resource-limited environments,” Ozcan said. “These results also constitute the first time that single nanoparticles and viruses have been detected using a cellphone-based, field-portable imaging system.”

The new research, published on Sept. 9 in the American Chemical Society’s journal ACS Nano, comes on the heels of Ozcan’s other recent inventions, including a cellphone camera–enabled sensor for allergens in food products and a smart phone attachment that can conduct common kidney tests.

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Nanodiamonds used to deliver chemotherapy drugs into brain tumors


Method found to have greater cancer-killing efficiency than existing treatments.

These images show the retention of doxorubicin and ND-DOX in brain tissue, with light microscopic images (upper rows) and fluorescence images detecting fluorescence generated from doxorubicin (lower rows). The images show the distribution of unmodified doxorubicin and ND-DOX after convection-enhanced delivery (CED) at 6, 16, 24 and 72 hours.

These images show the retention of doxorubicin and ND-DOX in brain tissue, with light microscopic images (upper rows) and fluorescence images detecting fluorescence generated from doxorubicin (lower rows). The images show the distribution of unmodified doxorubicin and ND-DOX after convection-enhanced delivery (CED) at 6, 16, 24 and 72 hours.

Researchers at UCLA’s Jonsson Comprehensive Cancer Center have developed an innovative drug-delivery system in which tiny particles called nanodiamonds are used to carry chemotherapy drugs directly into brain tumors. The new method was found to result in greater cancer-killing efficiency and fewer harmful side effects than existing treatments.

The research, published in the advance online issue of the peer-reviewed journal Nanomedicine: Nanotechnology, Biology and Medicine, was a collaboration between Dean Ho of the UCLA School of Dentistry and colleagues from the Lurie Children’s Hospital of Chicago and Northwestern University’s Feinberg School of Medicine. Ho co-directs UCLA Dentistry’s Weintraub Center for Reconstructive Biotechnology and is a professor in the division of oral biology and medicine, the division of advanced prosthodontics, and the department of bioengineering.

Glioblastoma is the most common and lethal type of brain tumor. Despite treatment with surgery, radiation and chemotherapy, the median survival time for glioblastoma patients is less than one-and-a-half years. The tumors are notoriously difficult to treat, in part because chemotherapy drugs injected alone often are unable to penetrate the system of protective blood vessels that surround the brain, known as the blood–brain barrier. And those drugs that do cross the barrier do not stay concentrated in the tumor tissue long enough to be effective.

The drug doxorubicin, a common chemotherapy agent, has shown promise in a broad range of cancers, and it has served as model drug for the treatment brain tumors when injected directly into the tumor. Ho’s team originally developed a strategy for strongly attaching doxorubicin molecules to nanodiamond surfaces, creating a combined substance called ND–DOX.

Nanodiamonds are carbon-based particles roughly 4 to 5 nanometers in diamter that can carry a broad range of drug compounds. And while tumor-cell proteins are able to eject most anticancer drugs that are injected into the cell before those drugs have time to work, they can’t get rid of the nanodiamonds. Thus, drug–nanodiamond combinations remain in the cells much longer without affecting the tissue surrounding the tumor.

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Creating a ‘window to the brain’


UC Riverside researchers develop novel transparent skull implant.

Members of the UC Riverside brain research team (from left): Javier Garay, Yasuhiro Kodera, Carissa L. Reynolds, Yasaman Damestani, Guillermo Aguilar, Masaru P. Rao and B. Hyle Park.

Members of the UC Riverside brain research team (from left): Javier Garay, Yasuhiro Kodera, Carissa L. Reynolds, Yasaman Damestani, Guillermo Aguilar, Masaru P. Rao and B. Hyle Park.

A team of UC Riverside researchers has developed a novel transparent skull implant that literally provides a “window to the brain,” which researchers hope will eventually open new treatment options for patients with life-threatening neurological disorders, such as brain cancer and traumatic brain injury.

The team’s implant is made of the same ceramic material currently used in hip implants and dental crowns, yttria-stabilized zirconia (YSZ). However, the key difference is that their material has been processed in a unique way to make it transparent.

Since YSZ has already proven itself to be well-tolerated by the body in other applications, the team’s advancement now allows use of YSZ as a permanent window through which doctors can aim laser-based treatments for the brain, importantly, without having to perform repeated craniectomies, which involve removing a portion of the skull to access the brain.

The work also dovetails with President Obama’s recently announced BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which aims to revolutionize the understanding of the human mind and uncover new ways to treat, prevent and cure brain disorders. The team envisions potential for their YSZ windows to facilitate the clinical translation of promising brain imaging and neuromodulation technologies being developed under this initiative.

“This is a case of a science fiction sounding idea becoming science fact, with strong potential for positive impact on patients,” said Guillermo Aguilar, a professor of mechanical engineering at UC Riverside’s Bourns College of Engineering.

Aguilar is part of 10-person team, comprised of faculty, graduate students and researchers from UC Riverside’s Bourns College of Engineering and School of Medicine, which recently published a paper “Transparent Nanocrystalline Yttria-Stabilized-Zirconia Calvarium Prosthesis” about its findings online in the journal Nanomedicine: Nanotechnology, Biology and Medicine.

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DARPA awards $6M to develop nanotech therapies for traumatic brain injuries


UC San Diego professor Michael Sailor leads multidisciplinary team.

DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.

Led by professor Michael J. Sailor, Ph.D., from UC San Diego, the award brings together a multidisciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D., of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D., of Massachusetts Institute of Technology; and Clark C. Chen, M.D., Ph.D., of UC San Diego School of Medicine.

Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.

“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.

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Ultrafine particles cause lung damage, study shows


Substances used in everything from paint to sporting equipment.

Kent Pinkerton, UC Davis

Kent Pinkerton, UC Davis

A consortium of scientists from across the country, including UC Davis, has found that breathing ultrafine particles from a large family of materials that increasingly are found in a host of household and commercial products, from sunscreens to the ink in copy machines to super-strong but lightweight sporting equipment, can cause lung inflammation and damage.

The research on two of the most common types of engineered nanomaterials is published online today in Environmental Health Perspectives, the journal of the National Institute of Environmental Health Sciences (NIEHS). It is the first multi-institutional study examining the health effects of engineering nanomaterials to replicate and compare findings from different labs across the country.

The study is critical, the researchers said, because of the large quantities of nanomaterials being used in industry, electronics and medicine. Earlier studies had found when nanomaterials are taken into the lungs they can cause inflammation and fibrosis. The unique contribution of the current study is that all members of the consortium were able to show similar findings when similiar concentrations of the materials were introduced into the respiratory system. The findings should provide guidance for creating policy for the safe development of nanotechnology.

“This research provides further confirmation that nanomaterials have the potential to cause inflammation and injury to the lungs. Although small amounts of these materials in the lungs do not appear to produce injury, we still must remain vigilant in using care in the diverse applications of these materials in consumer products and foods,” said Kent Pinkerton, a study senior author and the director of the UC Davis Center for Health and the Environment.”

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Nanosponges can remove toxins from bloodstream


Bactieral infections, E. coli, snake bites and bee stings neutralized in study of mice.

Engineers at UC San Diego have invented a “nanosponge” capable of safely removing a broad class of dangerous toxins from the bloodstream – including toxins produced by MRSA, E. coli, poisonous snakes and bees. These nanosponges, which thus far have been studied in mice, can neutralize “pore-forming toxins,” which destroy cells by poking holes in their cell membranes. Unlike other anti-toxin platforms that need to be custom synthesized for individual toxin type, the nanosponges can absorb different pore-forming toxins regardless of their molecular structures. In a study against alpha-haemolysin toxin from MRSA, pre-innoculation with nanosponges enabled 89 percent of mice to survive lethal doses. Administering nanosponges after the lethal dose led to 44 percent survival.

The team, led by nanoengineers at the UC San Diego Jacobs School of Engineering, published the findings in Nature Nanotechnology April 14.

“This is a new way to remove toxins from the bloodstream,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering and the senior author on the study. “Instead of creating specific treatments for individual toxins, we are developing a platform that can neutralize toxins caused by a wide range of pathogens, including MRSA and other antibiotic resistant bacteria,” said Zhang. The work could also lead to non-species-specific therapies for venomous snake bites and bee stings, which would make it more likely that health care providers or at-risk individuals will have life-saving treatments available when they need them most.

The researchers are aiming to translate this work into approved therapies. “One of the first applications we are aiming for would be an anti-virulence treatment for MRSA. That’s why we studied one of the most virulent toxins from MRSA in our experiments,” said “Jack” Che-Ming Hu, the first author on the paper. Hu, now a postdoctoral researcher in Zhang’s lab, earned his Ph.D. in bioengineering from UC San Diego in 2011.

Aspects of this work will be presented April 18 at Research Expo, the annual graduate student research and networking event of the UC San Diego Jacobs School of Engineering.

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