TAG: "Nanotechnology"

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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Nanodiamonds could improve effectiveness of breast cancer treatment


UCLA study shows versatility of nanodiamond as targeted drug-delivery agent to tumor site.

Nanodiamonds bound to the chemotherapy drug epirubicin are enclosed within a lipid membrane and coupled to antibodies specific to hard-to-treat tumors. These hybrid drug delivery agents cause tumors to regress in size while markedly improving drug tolerance.

Recently, doctors have begun to categorize breast cancers into four main groups according to the genetic makeup of the cancer cells. Which category a cancer falls into generally determines the best method of treatment.

But cancers in one of the four groups — called “basal-like” or “triple-negative” breast cancer (TNBC) — have been particularly tricky to treat because they usually don’t respond to the “receptor-targeted” treatments that are often effective in treating other types of breast cancer. TNBC tends to be more aggressive than the other types and more likely to recur, and can also have a higher mortality rate.

Fortunately, better drug therapies may be on the horizon. UCLA researchers and collaborators led by Dean Ho, a professor at the UCLA School of Dentistry and co-director of the school’s Jane and Jerry Weintraub Center for Reconstructive Biotechnology, have developed a potentially more effective treatment for TNBC that uses nanoscale, diamond-like particles called nanodiamonds.

Nanodiamonds are between 4 and 6 nanometers in diameter and are shaped like tiny soccer balls. Byproducts of conventional mining and refining operations, the particles can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs’ desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with triple negative breast cancer.

Findings from the study are published online today (April 15) in the peer-reviewed journal Advanced Materials.

“This study demonstrates the versatility of the nanodiamond as a targeted drug-delivery agent to a tumor site,” said Ho, who is also a member of the California NanoSystems Institute at UCLA, UCLA’s Jonsson Comprehensive Cancer Center and the UCLA Department of Bioengineering. “The agent we’ve developed reduces the toxic side effects that are associated with treatment and mediates significant reductions in tumor size.”

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Research on immune-cell therapy could strengthen promising cancer treatment


UCLA, Caltech researchers successfully monitor change in genetically modified T cells.

James Heath, UCLA

A new study of genetically modified immune cells by scientists from UCLA and the California Institute of Technology could help improve a promising treatment for melanoma, an often fatal form of skin cancer.

The research, which appears today (March 21) in the advance online edition of the journal Cancer Discovery, was led by James Heath, a member of UCLA’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and UCLA’s Jonsson Comprehensive Cancer Center. Heath is a professor of molecular and medical pharmacology at UCLA and also holds the Elizabeth W. Gilloon Chair in Chemistry at Caltech.

The melanoma treatment uses T cells — immune cells that play a major role in fighting infection — taken from patients with melanoma. The cells are then genetically modified in the laboratory so that when they are reintroduced into a patient’s bloodstream, they specifically attack melanoma tumors. In early clinical trials, this treatment was shown to shrink tumors dramatically in many patients, but the positive effects were often short-lived.

The UCLA and Caltech researchers found that after the engineered T cells were returned to patients, their efficacy faded within two to three weeks. Surprisingly, however, once the engineered cells were no longer effective, a new group of non-engineered T cells arose that had a similar tumor-killing effect that lasted even longer, the scientists discovered.

Using newly developed nanotechnology chips to perform multidimensional and multiplexed immune-monitoring assays, the researchers were able to examine at high resolution single engineered T cells taken at different times from patients undergoing the therapy, each of whom had a different level of response to the treatment.

“The engineered T cells did not recover their tumor-killing effect,” Heath said, “but after one month, another group of T cells appeared that did have tumor-killing effects for another 90 days. Those were not the genetically engineered T cells, and they appeared to be a byproduct of a process called ‘antigen spreading’ by the original engineered cells. After 90 days, those cells lost their tumor-killing ability as well.”

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‘NanoVelcro’ device refined to grab single cancer cells from blood


Improvement enables “liquid biopsies” for metastatic melanoma.

NanoVelcro chip

Researchers at UCLA report that they have refined a method they previously developed for capturing and analyzing cancer cells that break away from patients’ tumors and circulate in the blood. With the improvements to their device, which uses a Velcro-like nanoscale technology, they can now detect and isolate single cancer cells from patient blood samples for analysis.

Circulating tumor cells, or CTCs, play a crucial role in cancer metastasis, spreading from tumors to other parts of the body, where they form new tumors. When these cells are isolated from the blood early on, they can provide doctors with critical information about the type of cancer a patient has, the characteristics of the individual cancer and the potential progression of the disease. Doctors can also tell from these cells how to tailor a personalized treatment to a specific patient.

In recent years, a UCLA research team led by Hsian-Rong Tseng, an associate professor of molecular and medical pharmacology at the Crump Institute for Molecular Imaging and a member of both the California NanoSystems Institute at UCLA and UCLA’s Jonsson Comprehensive Cancer Center, has developed a “NanoVelcro” chip. When blood is passed through the chip, extremely small “hairs” — nanoscale wires or fibers coated with protein antibodies that match proteins on the surface of cancer cells — act like Velcro, traping CTCs and isolating them for analysis.

CTCs trapped by the chip also act as a “liquid biopsy” of the tumor, providing convenient access to tumor cells and earlier information about potentially fatal metastases.

Histopathology — the study of the microscopic structure of biopsy samples — is currently considered the gold standard for determining tumor status, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By being able to extract viable CTCs from the blood with the NanoVelcro chip, however, doctors can perform a detailed analysis of the cancer type and the various genetic characteristics of a patient’s specific cancer.

Tseng’s team now reports that they have improved the NanoVelcro chip by replacing its original non-transparent silicon nanowire substrate inside with a new type of transparent polymer nanofiber-deposited substrate, allowing the device’s nanowires to better “grab” cancer cells as blood passes by them.

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Researchers develop new therapeutics that could accelerate wound healing


UCLA scientists are working to take advantage of our body’s ability to heal itself.

Heather Maynard, UCLA

In “before” and “after” photos from advertisements for wound-healing ointments, bandages and antibiotic creams, we see an injury transformed from an inflamed red gash to smooth and flawless skin.

What we don’t appreciate is the vital role that our own natural biomolecules play in the healing process, including their contribution to the growth of new cells and the development of new blood vessels that provide nutrients to those cells.

Now, UCLA researchers led by Heather Maynard, a professor of chemistry and biochemistry and a member of UCLA’s California NanoSystems Institute, are working to take advantage of our body’s ability to heal itself by developing new bio-mimicking therapeutics that could be used to treat skin wounds.

Among the key players involved in natural wound-healing is a signaling molecule known as basic fibroblast growth factor, or bFGF, which is secreted by our cells to trigger processes that are involved in healing, as well as embryonic development, tissue regeneration, bone regeneration, the development and maintenance of the nervous system, and stem cell renewal.

BFGF has been widely investigated as a tool doctors could potentially use to promote or accelerate these processes, but its instability outside the body has been a significant hurdle to its widespread use, Maynard said.

Now, Maynard and her team have discovered how to stabilize bFGF based on the principle of mimicry. Relying on the growth factor’s ability to bind heparin — a naturally occurring complex sugar found on the surface of our cells — the team synthesized a polymer that mimics the structure of heparin. When attached to bFGF, the new polymer makes the protein stable to the many stresses that normally inactivate it, rendering it a more suitable candidate for medical applications.

The research is published Feb. 17 in the online edition of the journal Nature Chemistry and will appear in an upcoming print edition of the journal.

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Microscopes detect viruses, other objects at nanoscale


UCLA invention could be useful for diagnosis where medical resources are limited.

Nano-lens image of H1N1 flu virus

Nano-lens image of H1N1 flu virus

By using tiny liquid lenses that self-assemble around microscopic objects, a team from UCLA‘s Henry Samueli School of Engineering and Applied Science has created an optical microscopy method that allows users to directly see objects more than 1,000 times smaller than the width of a human hair.

Coupled with computer-based computational reconstruction techniques, this portable and cost-effective platform, which has a wide field of view, can detect individual viruses and nanoparticles, making it potentially useful in the diagnosis of diseases in point-of-care settings or areas where medical resources are limited.

Electron microscopy is one of the current gold standards for viewing nanoscale objects. This technology uses a beam of electrons to outline the shape and structure of nanoscale objects. Other optical imaging–based techniques are used as well, but all of them are relatively bulky, require time for the preparation and analysis of samples, and have a limited field of view — typically smaller than 0.2 square millimeters — which can make viewing particles in a sparse population, such as low concentrations of viruses, challenging.

To overcome these issues, the UCLA team, led by Aydogan Ozcan, an associate professor of electrical engineering and bioengineering, developed the new optical microscopy platform by using nanoscale lenses that stick to the objects that need to be imaged. This lets users see single viruses and other objects in a relatively inexpensive way and allows for the processing of a high volume of samples.

“This work demonstrates a high-throughput and cost-effective technique to detect sub–100-nanometer particles or viruses over very large sample areas,” said Ozcan, who is also a member of the California NanoSystems Institute and holds a faculty appointment in the department of surgery at the David Geffen School of Medicine at UCLA. “It is enabled by a unique combination of surface chemistry and computational imaging.”

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New drug delivery system developed for bladder cancer


UC Davis researchers use nanoparticles to produce more effective cancer control.

Chong-Xian Pan, UC Davis

A team of UC Davis scientists has shown in experimental mouse models that a new drug delivery system allows for administration of three times the maximum tolerated dose of a standard drug therapy for advanced bladder cancer, leading to more effective cancer control without increasing toxicity.

The delivery system consists of specially designed nanoparticles that home in on tumor cells while carrying the anti-cancer drug paclitaxel. The same delivery system also was successfully used to carry a dye that lights up on imaging studies, making it potentially useful for diagnostic purposes. The findings are published today in the journal Nanomedicine.

“We have developed a novel, multifunctional nanotherapeutics platform that can selectively and efficiently deliver both diagnostic and therapeutic agents to bladder tumors,” said Chong-Xian Pan, principal investigator of the study and associate professor of  hematology and oncology at UC Davis. “Our results support its potential to be used for both diagnostic and therapeutic applications for advanced bladder cancer.”

Cancer of the bladder usually develops in the cells of the inner lining of the bladder. Survival rates are high if the disease is caught early, but it remains difficult to treat in advanced stages ― when the tumor has grown outside of the bladder or metastasized to distant sites. It is the fourth most common cancer in men; it occurs less frequently in women.

Kit Lam, UC Davis

Paclitaxel is a drug used to treat advanced bladder cancer and other cancers, but it is associated with serious safety concerns. It can be toxic to bone marrow, leading to reduced levels of red and white blood cells, putting patients at risk of infection. In addition, because the drug is not readily soluble in blood, it is typically dissolved in castor oil, which has caused severe ― and sometimes fatal ― allergic reactions.

The drug delivery system used in this study makes use of nanoparticles called micelles developed by Kit Lam, professor and chair of the UC Davis Department of Biochemistry and Molecular Medicine and a co-author of the article. Micelles are aggregates of soap-like molecules that naturally form a tiny spherical particle with a hollow center. The researchers incorporated specific targeting molecules ― called ligands ― into the micelle structure. These ligands, developed by UC Davis researchers, were successfully shown in earlier studies to preferentially bind to bladder cancer cells derived from dogs and humans.

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Nanoparticles detect biochemistry of inflammation


UC San Diego develops polymer designed to detect hydrogen peroxide.

Adah Almutairi, UC San Diego

Inflammation is the hallmark of many human diseases, from infection to neurodegeneration.  The chemical balance within a tissue is disturbed, resulting in the accumulation of reactive oxygen species (ROS) such as hydrogen peroxide, which can cause oxidative stress and associated toxic effects.

Although some ROS are important in cell signaling and the body’s defense mechanisms, these chemicals also contribute to and are indicators of many diseases, including cardiovascular dysfunction.  A non-invasive way of detecting measurable, low levels of hydrogen peroxide and other ROS would provide a viable way to detect inflammation. Such a method would also provide a way to selectively deliver drugs to their targets.

Adah Almutairi, PhD, associate professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, the Department of NanoEngineering, and the Materials Science and Engineering Program at the University of California, San Diego, and colleagues have developed the first degradable polymer that is extremely sensitive to low but biologically relevant concentrations of hydrogen peroxide.

Their work is currently published in the online issue of the Journal of the American Chemical Society.

These polymeric capsules, or nanoparticles, are taken up by macrophages and neutrophils – immune system cells that rush to the site of inflammation. The nanoparticles then release their contents when they degrade in the presence of hydrogen peroxide produced by these cells.

“This is the first example of a biocompatible way to respond to oxidative stress and inflammation,” said Almutairi, director of the UC San Diego Laboratory of Bioresponsive Materials. “Because the capsules are tailored to biodegrade and release their cargo when encountering hydrogen peroxide, they may allow for targeted drug delivery to diseased tissue.”

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