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Nano Cancer researchtest 030914Chemotherapy timing is key to success: Nanoparticles that stagger delivery of two drugs knock out aggressive tumors in mice.

Cambridge, MA | Posted on May 8th, 2014

 

 

Abstract:


MIT researchers have devised a novel cancer treatment that destroys tumor cells by first disarming their defenses, then hitting them with a lethal dose of DNA damage.

In studies with mice, the research team showed that this one-two punch, which relies on a nanoparticle that carries two drugs and releases them at different times, dramatically shrinks lung and breast tumors. The MIT team, led by Michael Yaffe, the David H. Koch Professor in Science, and Paula Hammond, the David H. Koch Professor in Engineering, describe the findings in the May 8 online edition of Science Signaling.

“I think it’s a harbinger of what nanomedicine can do for us in the future,” says Hammond, who is a member of MIT’s Koch Institute for Integrative Cancer Research. “We’re moving from the simplest model of the nanoparticle — just getting the drug in there and targeting it — to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumor.”

BioGraphene-320

Doctors routinely give cancer patients two or more different chemotherapy drugs in hopes that a multipronged attack will be more successful than a single drug. While many studies have identified drugs that work well together, a 2012 paper from Yaffe’s lab was the first to show that the timing of drug administration can dramatically influence the outcome.

In that study, Yaffe and former MIT postdoc Michael Lee found they could weaken cancer cells by administering the drug erlotinib, which shuts down one of the pathways that promote uncontrolled tumor growth. These pretreated tumor cells were much more susceptible to treatment with a DNA-damaging drug called doxorubicin than cells given the two drugs simultaneously.

“It’s like rewiring a circuit,” says Yaffe, who is also a member of the Koch Institute. “When you give the first drug, the wires’ connections get switched around so that the second drug works in a much more effective way.”

Erlotinib, which targets a protein called the epidermal growth factor (EGF) receptor, found on tumor cell surfaces, has been approved by the Food and Drug Administration to treat pancreatic cancer and some types of lung cancer. Doxorubicin is used to treat many cancers, including leukemia, lymphoma, and bladder, breast, lung, and ovarian tumors.

Staggering these drugs proved particularly powerful against a type of breast cancer cell known as triple-negative, which doesn’t have overactive estrogen, progesterone, or HER2 receptors. Triple-negative tumors, which account for about 16 percent of breast cancer cases, are much more aggressive than other types and tend to strike younger women.

That was an exciting finding, Yaffe says. “The problem was,” he adds, “how do you translate that into something you can actually give a cancer patient?”

From lab result to drug delivery

To approach this problem, Yaffe teamed up with Hammond, a chemical engineer who has previously designed several types of nanoparticles that can carry two drugs at once. For this project, Hammond and her graduate student, Stephen Morton, devised dozens of candidate particles. The most effective were a type of particle called liposomes — spherical droplets surrounded by a fatty outer shell.

The MIT team designed their liposomes to carry doxorubicin inside the particle’s core, with erlotinib embedded in the outer layer. The particles are coated with a polymer called PEG, which protects them from being broken down in the body or filtered out by the liver and kidneys. Another tag, folate, helps direct the particles to tumor cells, which express high quantities of folate receptors.

Once the particles reach a tumor and are taken up by cells, the particles start to break down. Erlotinib, carried in the outer shell, is released first, but doxorubicin release is delayed and takes more time to seep into cells, giving erlotinib time to weaken the cells’ defenses. “There’s a lag of somewhere between four and 24 hours between when erlotinib peaks in its effectiveness and the doxorubicin peaks in its effectiveness,” Yaffe says.

The researchers tested the particles in mice implanted with two types of human tumors: triple-negative breast tumors and non-small-cell lung tumors. Both types shrank significantly. Furthermore, packaging the two drugs in liposome nanoparticles made them much more effective than the traditional forms of the drugs, even when those drugs were given in a time-staggered order.

As a next step before possible clinical trials in human patients, the researchers are now testing the particles in mice that are genetically programmed to develop tumors on their own, instead of having human tumor cells implanted in them.

The researchers believe that time-staggered delivery could also improve other types of chemotherapy. They have devised several combinations involving cisplatin, a commonly used DNA-damaging drug, and are working on other combinations to treat prostate, head and neck, and ovarian cancers. At the same time, Hammond’s lab is working on more complex nanoparticles that would allow for more precise loading of the drugs and fine-tuning of their staggered release.

“With a nanoparticle delivery platform that allows us to control the relative rates of release and the relative amounts of loading, we can put these systems together in a smart way that allows them to be as effective as possible,” Hammond says.

Morton and Lee are the lead authors of the Science Signaling paper. Postdocs Zhou Deng, Erik Dreaden, and Kevin Shopsowitz, visiting student Elise Siouve, and graduate student Nisarg Shah also contributed to the research. The work was funded by the National Institutes of Health, the Center for Cancer Nanotechnology Excellence, and a Breast Cancer Alliance Exceptional Project Grant.

Written by Anne Trafton, MIT News Office

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Copyright © Massachusetts Institute of Technology

green earth untitledA BBC documentary on nanotechnology advances in Europe “Nano, The Next Dimension”

A very good video to provide “perspective” on how “All Things Nano” have ALREADY impacted our lives and how … the VAST (but tiny!) arena of “Nanotechnologies” (Nano: objects a billionth of a meter in size) will certainly impact ALL of the Sciences, Manufacturing, Communications and Consumer Materials. Impacts such as:

1.  Our abilities to capture and generate abundant renewable sources of energy, (Solar, Hydrogen Fuel Cells)

2. To create abundant sources of CLEAN WATER through vastly improved FILTRATION and WASTE REMEDIATION processes. (Desalination, Oil and Gas Fields)

3. To deliver LIFE SAVING Drug Therapies and provide vastly improved Diagnostics. (Diabetes, Cancer, Alzheimer’s)

4. To create FLEXIBLE SCREENS and PRINTABLE ELECTRONICS that offer vastly improved performance, user experience, with lower energy consumption and with significantly LOWER COSTS. (Flat Panel TV Screens, Smart Phones, Super-Computers, Super-Capacitors, Long-Lived Super Batteries)

5. Completely water, stain proof clothing. Lighter, Stronger Sports Equipment.

6. Coatings and Paints for Buildings, Windows and Highways that capture solar energy. Inks and Sensors that make our everyday life more Secure.

Through the month of January, we will be posting videos, articles and research summaries that focus on the coming accelerated “wave” of nano-supported technologies “that will change the way we innovate everything!”

“Great Things from Small Things!”

 

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A unique nanostructure developed by a team of international researchers, including those at the University of Cincinnati, promises improved all-in-one detection, diagnoses and drug-delivery treatment of cancer cells.

The first-of-its-kind nanostructure is unusual because it can carry a variety of cancer-fighting materials on its double-sided (Janus) surface and within its porous interior. Because of its unique structure, the nano carrier can do all of the following:

 

  • Transport cancer-specific detection nanoparticles and biomarkers to a site within the body, e.g., the breast or the prostate. This promises earlier diagnosis than is possible with today’s tools.
  • Attach fluorescent marker materials to illuminate specific cancer cells, so that they are easier to locate and find for treatment, whether drug delivery or surgery.
  • Deliver anti-cancer drugs for pinpoint targeted treatment of cancer cells, which should result in few drug side effects. Currently, a cancer treatment like chemotherapy affects not only cancer cells but healthy cells as well, leading to serious and often debilitating side effects.

This research, titled “Dual Surface Functionalized Janus Nanocomposites of Polystyrene//Fe304@Si02 for Simultaneous Tumor Cell Targeting and pH-Triggered Drug Release,” will be presented as an invited talk on Oct. 30, 2013, at the annual Materials Science & Technology Conference in Montreal, Canada. Researchers are Feng Wang, a former UC doctoral student and now a postdoc at the University of Houston; Donglu Shi, professor of materials science and engineering at UC’s College of Engineering and Applied Science (CEAS); Yilong Wang of Tongji University, Shanghai, China; Giovanni Pauletti, UC associate professor of pharmacy; Juntao Wang of Tongji University, China; Jiaming Zhang of Stanford University; and Rodney Ewing of Stanford University.

This recently developed Janus nanostructure is unusual in that, normally, these super-small structures (that are much smaller than a single cell) have limited surface. This makes is difficult to carry multiple components, e.g., both cancer detection and drug-delivery materials. The Janus nanocomponent, on the other hand, has functionally and chemically distinct surfaces to allow it to carry multiple components in a single assembly and function in an intelligent manner.

“In this effort, we’re using existing basic nano systems, such as carbon nanotubes, graphene, iron oxides, silica, quantum dots and polymeric nano materials in order to create an all-in-one, multidimensional and stable nano carrier that will provide imaging, cell targeting, drug storage and intelligent, controlled drug release,” said UC’s Shi, adding that the nano carrier’s promise is currently greatest for cancers that are close to the body’s surface, such as breast and prostate cancer.

If such nano technology can someday become the norm for cancer detection, it promises earlier, faster and more accurate diagnosis at lower cost than today’s technology. (Currently, the most common methods used in cancer diagnosis are magnetic resonance imaging or MRI; Positron Emission Tomography or PET; and Computed Tomography or CT imaging, however, they are costly and time consuming to use.)

In addition, when it comes to drug delivery, nano technology like this Janus structure, would better control the drug dose, since that dose would be targeted to cancer cells. In this way, anticancer drugs could be used much more efficiently, which would, in turn, lower the total amount of drug administered.

Source: University of Cincinnati

carbon-nanotube(Nanowerk News) Graphene holds potential for diverse applications, including battery materials, electrodes, high-speed electronics, water filtration, and solar energy harvesting. We’ve discussed most of those applications in earlier blog posts, and not a day passes without some progress in one of those directions hitting the world headlines. Little media attention, however, has been paid to a young and exciting application of graphene – oil exploration.
Most of the world’s growing energy demand is fulfilled from some form of fossil fuel, like coal and oil. It is well known that oil exploration and the energy sector are big business, but also potentially damaging to the environment. Oil spills and uncontrolled oil well explosions form just a part of the risk involved in oil exploration. Another cause for concern is the efficiency of extraction, and potential losses, or leaks of oil into the environment. Graphene is being explored for its use in various stages of the exploration and extraction process.
Much of the research on graphene for oil has come out of the lab of Prof. James Tour at Rice University. In their early work (published in 2012: “Graphene Oxide as a High-Performance Fluid-Loss-Control Additive in Water-Based Drilling Fluids”), the group first showed that adding platelets of graphene oxide to a common water-based drilling fluid decreased the losses of the fluid to the surrounding rock, as compared to a standard mixture of clays and polymers used in the drilling industry today.
Graphene platelet plugging a nanopore
Graphene platelet plugging a nanopore (from ACS Applied Materials and Interfaces 4, 222 (2012))
These fluids are pumped downhole as part of the process to keep drill bits clean and remove cuttings. With traditional clay-enhanced fluids, differential pressure forms a layer on the wellbore called a filter cake, which both keeps the oil from flowing out and drilling fluids from invading the tiny, oil-producing pores.
When the drill bit is removed and drilling fluid displaced, the formation oil forces remnants of the filter cake out of the pores as the well begins to produce. But sometimes the clay won’t budge, and the well’s productivity is reduced.
The Tour Group discovered that microscopic, pliable flakes of graphene can form a thinner, lighter filter cake (“Functionalized graphene oxide plays part in next-generation oil-well drilling fluids”). When they encounter a pore, the flakes fold in upon themselves and look something like starfish sucked into a hole. But when well pressure is relieved, the flakes are pushed back out by the oil. The thinner graphene layer budged much more easily than the the layer which would remain after a traditional clay-enhanced liquid was used. A drilling fluid with 2 percent functionalized graphene oxide formed a filter cake an average of 22 micrometers wide — substantially smaller than the 278-micrometer cake formed by traditional drilling fluids. GO blocked pores many times smaller than the flakes’ original diameter by folding.
Graphene can also be put to use for well logging. Well logging techniques provide data on the geological properties of reservoirs of interest to the oil and gas exploration industry. A commonly used logging technique uses wirelines to provide information about an oil or gas well. Wirelines are long wires with sensors attached to them, which are lowered into an exploration hole to provide information about the hole and its contents. An extension of wireline logging is logging-while-drilling, which relies on sensors at the end of the drill itself. Both methods utilize oil-based fluids for drilling and lubrication. Oil-based fluids, however, are not very good conductors of electricity, which is where graphene enters the scene. The group of Tour developed a solution that contains magnetic graphene nanoribbons (MGNRs). The MGNRs form part of a conductive coating in oil-based drilling fluids, improving the reliability of the information that is sent back up the hole by the sensors. Furthermore, the magnetic properties of the ribbons could also be exploited for using the ribbons themselves as advanced sensors. The Tour group filed a patent for this application.
Finally, since graphene nanoribbons can be made small enough to pass into tiny crevices of the rock which holds precious oil, some envision little graphene-based robots creeping through rocks, sending wireless data which contains information on oil location and concentration.
Source: By  Marko Spasenovic, Graphenea

Read more: http://www.nanowerk.com/nanotechnology_news/newsid=33733.php#ixzz2nlSIv0fw


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