Tag: UC Davis

Ending Cancer: Cancer-Hunting Nanoparticles

cancer_hunting_nanoparticleWhen it comes to diseases and conditions that have long been thought to be incurable – i.e. cancer, diabetes, HIV – nanoparticles are making a big impact. In the case of HIV, solutions have been developed where gold nanoparticles can deliver bee venom or HIV medication to cells of the virus, while leaving healthy tissue alone. As for diabetes and cancer, the same concept has proven useful at both seeking out and delivering medication to the requisite cells.

However, a new breakthrough may be offering cancer patients something more in the coming years. In what appears to be a promising development, researchers at the University of California Davis (UC Davis) Cancer Center have created a multi-tasking nanoparticle shown to be effective both in the diagnosis of a tumor and attacking its cells – a flexibility that could lead to new treatment options for cancer patients.

gold_nanoparticlesOne of the big challenges in developing multitasking nanoparticles is that they are traditional designed with one purpose in mind. They are constructed using either inorganic or organic compounds, each with strengths of their own. Inorganic nanoparticles, such those made from gold, are effective in imaging and diagnostics. Organic nanoparticles, on the other hand, are biocompatible and provide a safe method of drug delivery.

The nanoparticles developed at UC Davis are made from a polymer composed of organic compounds porphyrin and cholic acid, which is produced by the liver. The researchers then added cysteine – an amino acid that prevents it from releasing its payload prematurely – to create a fluorescent carbon nanoparticle (CNP). The team then tested the new nanoparticle with a range of tasks, both in vitro and in vivo (aka. in a solution of cells and in living organisms).

cancer_killing_laserThey found the particle was effective in delivering cancer-fighting drugs such as doxorubicin (commonly used in chemotherapy). In addition, they found that while applying light (known as photodynamic therapy), the nanoparticles release reactive molecules called singlet oxygen that destroy tumor cells, while heating them with a laser (known as photothermal therapy) provided another way for the particles to destroy tumors.

One notable finding was that the release of a payload sped up as the nanoparticle was exposed to light. The researchers claim this ability to manipulate the rate at which the particles release chemotherapy drugs from inside the tumor could help to minimize toxicity. This is a big plus considering that all known cancer treatments – i.e. chemotherapy, medication, radiation – all come with side effects and have a high risk causing damage to the patient’s healthy tissue.

NanoparticlesIn relation to imaging and phototherapy, the nanoparticle remained in the body for extended periods and bonded with imaging agents. And because CNPs are drawn more to tumor tissue than normal tissue, it helps to improve contrast and light them up for MRI and PET scans. This effectively makes the UC Davis nanoparticle a triple threat as far as cancer treatments are concerned.

As Yuanpei Li, research faculty member from the UC Davis Cancer Center, explains it:

This is the first nanoparticle to perform so many different jobs. From delivering chemo, photodynamic and photothermal therapies to enhancing diagnostic imaging, it’s the complete package.

The team is now focusing on further pre-clinical studies, with a view to advancing to human trials if all goes to plan. And this is not the only breakthrough inolving cancer-fighting nanoparticles to be made in recent months. Back in April, scientists at MIT reported the creation a revolutionary building block technique that’s enabled them to load a nanoparticle with three drugs, and claim it could be expanded to allow one to carry hundreds more.

MIT_nanoparticleTypical nanoparticle designs don’t allow for scaling, since they call for building a nanoparticle first, then encapsulating the drug molecules within it or chemically attaching the molecules to it. Attempting to add more drugs makes assembling the final nanoparticle exponentially more difficult. To overcome these limitations, Jeremiah Johnson, an assistant professor of chemistry at MIT, created nanoparticle building blocks that already included the desired drug.

Called “brush first polymerization,” the approach allows the researchers to incorporate many drugs within a single nanoparticle and control the precise amounts of each. In addition to the drug, each tiny building block contains a linking unit enabling it to easily connect to other blocks, and a protective compound to ensure that the drug stays intact until it enters the cell.

MIT_nanoparticle1The approach not only allows different drug-containing blocks to be assembled into specific structures, but it also enables each drug to be released separately via different triggers. The team has tested its triple threat nanoparticles, containing drugs typically used to treat ovarian cancer – such as doxorubicin, cisplatin and camptothecin – against lab-grown ovarian cancer cells.

The results demonstrated the new nanoparticles’ ability to destroy cancer cells at a higher rate than those carrying fewer drugs. As Johnson explained it:

This is a new way to build the particles from the beginning. If I want a particle with five drugs, I just take the five building blocks I want and have those assemble into a particle. In principle, there’s no limitation on how many drugs you can add, and the ratio of drugs carried by the particles just depends on how they are mixed together in the beginning… We think it’s the first example of a nanoparticle that carries a precise ratio of three drugs and can release those drugs in response to three distinct triggering mechanisms.

In this case, the cisplatin is delivered the instant the particle enters the cell, as it reacts to the presence of an antioxidant found in the cells called glutathione. When the nanoparticle encounters a cellular enzyme called esterases it releases the second drug, camptothecin. Shining ultraviolet light triggers the release of the remaining doxorubicin, leaving behind only the biodegradable remnants of the nanoparticle.

nanoparticle_cancertreatmentThe researchers believe this approach can potentially be used to link hundreds of building blocks to create multidrug-carrying nanoparticles, and pave the way for entirely new types of cancer treatments, free from the damaging side effects that accompany traditional chemotherapy. The MIT team is currently working on making nanoparticles that can deliver four drugs, and are also engaged in tests that treat tumor cells in animals.

Until recently, the fight against cancer has been characterized by attrition. While treatments exist, they tend to be a balancing act – inflicting harm and poisoning the patient in small doses with the hope of killing the cancer and not the host. Smarter treatments that target the disease while sparing the patient from harm are just what is needed to turn the tide in this fight and bring cancer to an end.

Sources: gizmag.com, (2), nature.com, ucdmc.ucdavis.edu

News from Mars: Martian Water and Earth Organisms

curiosity_peakThis August, the Curiosity Rover will be celebrating its second anniversary of roving around the Red Planet. And ever since it made landfall, Curiosity and the Mars Science Laboratory has repeatedly uncovered signs that Mars was once very like Earth. Basically, it has become undeniable that water once flowed freely over the surface of this barren and uninhabitable world. And this finding, much to the delight of futurists and sci-fi enthusiasts everywhere, is likely to pave the way for human settlement.

Liquid water disappeared from Mars’ surface millions of years ago, leaving behind tantalizing clues about the planet’s ancient past—clues that the MSL has been deciphering for the past 22 months. This began last year when Curiosity found rounded pebbles in the Glenelg region, an indication that a stream once flowed at the site. This was followed by the discovery of rocky outcroppings where the remains of an ancient stream bed consisting of water-worn gravel that was washed down from the rim of Gale Crater.

mountsharp_galecraterThe rover has since moved to a location about 6.5 kilometers (4 miles) away from the Gale Crater landing site, where scientists expect to make even more discoveries. The new location is named Kimberly, after a region of northwestern Australia. As Dawn Sumner, a UC Davis geology professor and co-investigator for NASA’s Mars Science Laboratory team, explained:

Our findings are showing that Mars is a planet that was once a whole lot like Earth. All the rocks we’ve seen on this mission are sediments that have been deposited by water. We’ve found almost no sandstone deposited by wind.

Sumner is working from Curiosity mission control at NASA’s Jet Propulsion Laboratory in Pasadena while on sabbatical from UC Davis, exploring whether the planet ever had an environment capable of supporting microbial life. She is also one of several UC scientists and engineers who have been vital to the success of the Curiosity mission, which is part of NASA’s long-term plan to pave the way for sending astronauts to Mars.

Living-Mars.2In that vein, research continues here on Earth to see exactly what kind of life can survive in the harsh Martian environment. And now,  research suggests that methanogens – among the simplest and oldest organisms on Earth – could survive on Mars. These microorganisms are typically found in swamps and marshes, where they use hydrogen as their energy source and carbon dioxide as their carbon source to produce methane (aka. natural gas).

As an anaerobic bacteria, methanogens don’t require require oxygen or organic nutrients to live, and are non-photosynthetic. Hence, they would be able to exist in sub-surface environments and would therefore be ideal candidates for life on Mars. Rebecca Mickol, a doctoral student in space and planetary sciences at the University of Arkansas, subjected two species of methanogens to Martian conditions to see how they would fair on the Red Planet.

methanogens485These strains included Methanothermobacter wolfeii and Methanobacterium formicicum, both of which survived the Martian freeze-thaw cycles that Mickol replicated in her experiments. This consisted of testing the species for their ability to withstand Martian freeze-thaw cycles that are below the organisms’ ideal growth temperatures. As she explained it:

The surface temperature on Mars varies widely, often ranging between minus 90 degrees Celsius and 27 degrees Celsius over one Martian day. If any life were to exist on Mars right now, it would at least have to survive that temperature range. The survival of these two methanogen species exposed to long-term freeze/thaw cycles suggests methanogens could potentially inhabit the subsurface of Mars.

Mickol conducted the study with Timothy Kral, professor of biological sciences in the Arkansas Center for Space and Planetary Sciences and lead scientist on the project. She presented her work at the 2014 General Meeting of the American Society for Microbiology, which was held from May 17th to 20th in Boston.

maven_atmosphereThe two species were selected because one is a hyperthermophile, meaning it thrives under extremely hot temperatures, and the other is a thermophile, which thrives under warm temperatures. Since the 1990s, Kral has been studying methanogens and examining their ability to survive on Mars. In 2004, scientists discovered methane in the Martian atmosphere, and immediately the question of the source became an important one. According to Kral:

When they made that discovery, we were really excited because you ask the question ‘What’s the source of that methane?. One possibility would be methanogens.

Understanding the makeup of Mars atmosphere and ecology is another major step towards ensuring that life can exist there again someday. From Red Planet, to Blue Planet, to Green Planet… it all begins with a fundamental understanding of what is currently able to withstand the Martian environment. And once this foundation is secured, our ecologists and environmental engineers can begin contemplating what it will take to create a viable atmosphere and sustainable sources of water there someday.

terraformingSources: phys.org, (2)