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

The Future is Here: Cancer Drug Developed by AI

AI'sThe development of cancer drugs is a costly, expensive, time-consuming process that has a high probability rate of failure. On average, it takes 24 to 48 months to find a suitable candidate and costs upwards of $100 million. And in the end, roughly 95% of all potential drugs fail in clinical trials. Because of this, scientists are understandably looking for a way to speed up the discovery process.

That’s where the anti-cancer drug known as BPM 31510 comes in play. Unlike most pharmaceuticals, it was developed by artificial intelligence instead of a group of researchers toiling away in a lab. Created by biotech company Berg (named after real estate billionaire Carl Berg) the company seeks to use artificial intelligence to design cancer drugs that are cheaper, have fewer side effects, and can be developed in half the time it normally takes.

drugsTowards this end, they are looking to data-driven methods of drug discovery. Instead of generating cancer drugs based on chemical compounds identified in labs, the company compares tissue, urine, and blood samples from cancer patients and healthy patients, generating tens of trillions of data points that are fed into an artificial intelligence system. That system crunches all the data, looking for problems.

BPM 31510, which is the first of Berg’s drugs to get a real-world test, focuses on mitochondria – a framework within cells that’s responsible for programmed cell death. Normally, mitochondria triggers damaged cells to die. When cancer strikes, this process goes haywire, and the damaged cells spread. Berg’s drug, if successful, will be able to restore normal cell death processes by changing the metabolic environment within mitochondria.

MitochondriaSpeaking on the subject of the drug, which is now in human-clinical trials, Berg president and co-founder Niven Narain said:

BPM 31510 works by switching the fuel that cancer likes to operate on. Cancer cells prefer to operate in a less energy-efficient manner. Cancers with a high metabolic function, like triple negative breast cancer, glioblastoma, and colon cancer–that’s the sweet spot for this technology.

IBM is also leveraging artificial intelligence in the race to design better cancer treatments. In their case, this involves their much-heralded supercomputer Watson looking for better treatment options for patients. In a trial conducted with the New York Genome Center, Watson has been scanning mutations found in brain cancer patients, matching them with available treatments.

dna_cancerAll of these efforts are still in early days, and even on its accelerated timeline, BPM 31510 is still years away from winning an FDA approval. But, as Narain points out, the current drug discovery system desperately needs rethinking. With a success rate of 1 out of 20, their is definitely room for improvement. And a process that seeks to address cancer in a way that is more targeted, and more personalized is certainly in keeping with the most modern approaches to medicine.

Source: fastcoexist.com

Nanotech News: Tiny Propellers for Drug Delivery

NanopropellersThe scientific and medical research communities have been looking to develop robots that measure in the nanometer range (that’s one-billionth of a meter) for quite some time. Being so small, they would be able to perform difficult tasks, such as targeted drug delivery to specific cells, or the elimination of harmful antigens, pathogens or viruses. However, the development of such machines raises numerous challenges.

For one, making them small enough to fit between cells remains tricky, and these tiny bots would also need a propulsion system that will allow them to navigate their way through the human body. But now, in a paper published in the June 2014 issue of ACS Nano, an Israeli and German team announced the creation of the smallest nanobot yet, a magnet-guided corkscrew which is propelled by a tiny helical propeller.

Nanopropellers1The team is comprised of researchers from the Technion-Israel Institute of Technology, the Max Planck Institute for Intelligent Systems, and the Institute for Physical Chemistry at the University of Stuttgart, Germany. Led by Dr. Peer Fischer at the Max Planck Institute, the research team created the tiny helical nanopropeller from a filament of silica and nickel that measures just 70 nanometers in diameter and 400 in length.

That’s more than 1,000 times smaller than the width of a human hair, or 100 times smaller than a single red blood cell, making the wee machine the tiniest nanopropeller humanity has ever created. Instead of carrying its own motor, the propeller is powered by an externally-applied weak rotating magnetic field which causes the prop to spin, driving it and its attached payload forward.

nanotech-2In order to test it, the scientist placed it in a hyaluronan gel, which is similar in consistency to bodily fluids. Like those fluids, the gel contains a mesh of entangled long polymer protein chains. In previous studies, larger micrometer-sized propellers got caught in these chains, slowing or completely halting their progress. The new nanoprop, however, was able to move relatively quickly by simply passing through the gaps in the mesh.

The study’s co-author, Associate Professor Alex Leshanksy of the Technion Faculty of Chemical Engineering, said that the nanobots:

actually display significantly enhanced propulsion velocities, exceeding the highest speeds measured in glycerin as compared with micro-propellers, which show very low or negligible propulsion.

The applications for this device certainly include targeted drug delivery, where the nanobots would be equipped with insulin, antibiotics, or even chemotherapy drugs which they could then deliver to specific cells in the body to speed up the delivery process and reduce side-effects. Scientists could also attach “active molecules” to the tips of the propellers, or use the propellers to deliver tiny doses of radiation.

nanobotsThe applications seem wide, varied, and exciting, from combating diabetes to fighting cancer and HIV with surgical precision. And developments like these, though they measure in the billionth of meters, they add up to a future where lives are healthier, longer and more prosperous.

Sources: engadget.com, gizmag.com, ats.org

The Future of Medicine: New Cancer Tests and Treatments

cancer_growingWhile a cure for cancer is still beyond medical science, improvements in how we diagnose and treat the disease are being made every day. These range from early detection, which makes all the difference in preventing the spread of the disease; to less-invasive treatments, which makes for a kinder, gentler recovery. By combining better medicine with cost-saving measures, accessibility is also a possibility.

When it comes to better diagnostics, the aim is to find ways to detect cancer without harmful and expensive scans or exploratory surgery. An alternative is a litmus test, like the one invented by Jack Andraka to detect pancreatic cancer. His method, which was unveiled at the 2012 Intel International Science and Engineering Fair (ISEF), won him the top prize due to the fact that it’s 90% accurate, 168 times faster than current tests and 1/26,000th the cost of regular tests.

cancer_peetestSince that time, Jack and his research group (Generation Z), have been joined by such institutions as MIT, which recently unveiled a pee stick test to detect cancer. In research published late last month in the Proceedings of the National Academy of Sciences, MIT Professor Sangeeta Bhatia reported that she and her team developed paper test strips using the same technology behind in-home pregnancy tests, ones which were able to detect colon tumors in mice.

The test strips work in conjunction with an injection of iron oxide nanoparticles, like those used as MRI contrast agents, that congregate at tumor sites in the body. Once there, enzymes known as matrix metalloproteinases (MMPs), which cancer cells use to invade healthy tissue, break up the nanoparticles, which then pass out through the patient’s urine. Antibodies on the test strip grab them, causing gold nanoparticles to create a red color indicating the presence of the tumor.

cancer_peetest2According to Bhatia, the technology is likely to make a big splash in developing countries where complicated and expensive medical tests are a rarity. Closer to home, the technology is also sure to be of significant use in outpatient clinics and other decentralized health settings. As Bhatia said in a press release:

For the developing world, we thought it would be exciting to adapt (the technology) to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.

To help Bhatia and her research team to bring her idea to fruition, MIT has given her and her team a grant from the university’s Deshpande Center for Technological Innovation. The purpose of the grant is to help the researchers develop a startup that could execute the necessary clinical trials and bring the technology to market. And now, Bhatia and her team are working on expanding the test to detect breast, prostate cancers, and all other types of cancer.

?????????????In a separate but related story, researchers are also working towards a diagnostic methods that do not rely on radiation. While traditional radiation scanners like PET and CT are good at finding cancer, they expose patients to radiation that can create a catch-22 situation where cancer can be induced later in life, especially for younger patients. By potentially inducing cancer in young people, it increases the likelihood that they will have to be exposed to more radiation down the line.

The good news is that scientists have managed to reduce radiation exposure over the past several years without sacrificing image quality. But thanks to ongoing work at the Children’s Hospital of Michigan, the Stanford School of Medicine, and Vanderbilt Children’s Hospital, there’s a potential alternative that involves combining MRI scans with a contrast agent, similar to the one Prof. Bhatia and her MIT group use in their peestick test.

cancer_braintumorAccording to a report published in the journal The Lancet Oncology, the researchers claimed that the new MRI approach found 158 tumors in twenty-two 8 to 33-year-olds, compared with 163 found using the traditional PET and CT scan combo. And since MRIs use radio waves instead of radiation, the scans themselves have no side effects. While the study is small, the positive findings are a step toward wider-spread testing to determine the effectiveness and safety of the new method.

The next step in testing this method will be to study the approach on more children and investigate how it might work in adults. The researchers say physicians are already launching a study of the technique in at least six major children’s hospitals throughout the country. And because the cost of each method could be roughly the same, if the MRI approach proves just as effective yet safer, radiation-free cancer scans are likely to be the way of the future.

cancer_georgiatechAnd last, but not least, there’s a revolutionary new treatment pioneered by researchers at Georgia Tech that relies on engineered artificial pathways to lure malignant cells to their death. This treatment is designed to address brain tumors – aka. Glioblastoma multiform cancer (GBM) – which are particularly insidious because they spread through the brain by sliding along blood vessels and nerve passageways (of which the brain has no shortage of!)

This capacity for expansion means that sometimes tumors developed in parts of the brain where surgery is extremely difficult – if not impossible – or that even if the bulk of a tumor can be removed, chances are good its tendrils would still exist throughout the brain. That is where the technique developed by scientists at Georgia Tech comes in, which involves creating artificial pathways along which cancer can travel to either more operable areas or even to a deadly drug located in a gel outside the body.

cancer_georgiatech1According to Ravi Bellamkonda, lead investigator and chair of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University:

[T]he cancer cells normally latch onto … natural structures and ride them like a monorail to other parts of the brain. By providing an attractive alternative fiber, we can efficiently move the tumors along a different path to a destination that we choose.

The procedure was reported in a recent issue of the journal Nature Materials. It involved Bellamkonda and his team implanting nanofibers about half the size of a human hair in rat brains where GBMs were growing. The fibers were made from a polycaprolactone (PCL) polymer surrounded by a polyurethane carrier and mimicked the contours of the nerves and blood vessels cancer cells like to use as a biological route.

cancer_georgiatech2One end of a fiber was implanted into the tumor inside the brain and the other into a gel containing the drug cyclopamine (which kills cancer cells) outside the brain. After 18 days, enough tumor cells had migrated along the fiber into the gel to shrink the tumor size 93 percent. Not only does Bellamkonda think his technique could be used to relocate and/or destroy cancers, he says he believes it could be used to help people live with certain inoperable cancers as a chronic condition.

In a recent statement, Bellakomba had this to say about the new method and the benefits its offers patients:

If we can provide cancer an escape valve of these fibers, that may provide a way of maintaining slow-growing tumors such that, while they may be inoperable, people could live with the cancers because they are not growing. Perhaps with ideas like this, we may be able to live with cancer just as we live with diabetes or high blood pressure.

Many of today’s methods for treating cancer focus on using drugs to kill tumors. The Georgia Tech team’s approach was engineering-driven and allows cancer to be treated with a device rather than with chemicals, potentially saving the patient many debilitating side effects. Part of the innovation in the technique is that it’s actually easier for tumors to move along the nanofibers than it is for them to take their normal routes, which require significant enzyme secretion as they invade healthy tissue.

cancer_georgiatech3Anjana Jain, the primary author of the study, was also principally responsible for the design of the nanofiber technique. After doing her graduate work on biomaterials used for spinal cord regeneration, she found herself working in Bellamkonda’s lab as a postdoctoral fellow and came up with the idea of routing materials using engineered materials. In a recent statement, she said the following of her idea:

Our idea was to give the tumor cells a path of least resistance, one that resembles the natural structures in the brain, but is attractive because it does not require the cancer cells to expend any more energy.

Extensive testing, which could take up to 10 years, still needs to be conducted before this technology can be approved for use in human patients. In the meantime, Bellamkonda and his team will be working towards using this technology to lure other cancers that like to travel along nerves and blood vessels. With all the advances being made in diagnostics, treatments, and the likelihood of a cure being found in the near future, the 21st century is likely to be the era where cancer becomes history.

Sources: news.cnet.com, (2), (3)

Ending Cancer: “Computational Cell Biology”

Cancer-researcherOne doesn’t think that diseases themselves would be vulnerable to infections; in fact, it seems counter-intuitive at best. And yet, that is what a group of scientists from Ottawa, Ontario (my old hometown) are proposing. Using and advanced mathematical modeling system to engineer viruses that will infect and destroy cancer cells, the team has been investigating how treatment techniques and genetic modification might allow cancer-killing (oncolytic) viruses to overcome cancer cells’ anti-infection defenses and kill them.

In a report filed with Nature Communication magazine, the lead authors – Dr. Mads Kaern and Dr. John Bell, a medical researcher and senior biologist from the University of Ottawa – detailed how the team used mathematical modeling to create techniques to render cancer cells highly vulnerable to infection while leaving healthy tissue untouched. The modified oncolytics zero in on the very thing that makes cancer cells so destructive — their potential to proliferate and grow explosively and unchecked, and blocks it.

dnacomputingCancer cells and normal cells are equipped with defensive mechanisms that protect them from invading cells. By using mathematical models, the Ottawa team has managed to equip oncolytic viruses with a gene that helps them override many kinds of cancer cells’ natural defenses, slowing the cancer’s reproduction and also making it more vulnerable to other infections.

Kaern and Bell constructed a mathematical model of the process of infection of a cancer cell, including how the virus would replicate, spread itself and override the cancer’s biological defenses. The study used predictive models to understand how the viruses might better overcome the cancer’s defenses, models that turned out to be surprisingly accurate.

cancer_cellIn an interview with Raw Story, Kaern explained the process and how it works:

These viruses tend to replicate better in cancer cells, because cancer cells tend to grow and divide more with an increased metabolism. The viruses are sort of exploiting that by replicating more aggressively, specifically in cancer cells.

The trick, Kaern said, is to engineer viruses that do that, but with minimal harm to surrounding healthy cells. The engineered viruses are built to not propagate in healthy tissues. But when it comes to cancer cells, it only takes one oncolytic virus making contact with one cancer cell to begin the propagation process.

chemotherapy2The benefits of this kind of treatment are obvious and profound. In addition to being self-propagating, it will also eliminate the need for expensive and unhealthy treatment:

You don’t really have to overload the system with tons of chemotherapy, which also targets specific cancers, right? But you have to ingest these large amounts intravenously and people get really sick from that because all the cells in the body are affected. So the advantage of the viruses is that they will find where they have to go and you only need one to start to process.

Of course, their is still a great deal to learn though. As Kaern points out, “cancer is a very complicated and diverse disease, and some viruses work well in some circumstances and not well in others.” While a “magic bullet” anti-cancer panacea is probably not going to arise in the near future, the use of mathematical modeling is speeding up the research process and opening up exciting possibilities.

Source: rawstory.com

Ending Cancer: “Canary” and Microscopic Velcro

cancer_cellEnding terminal illness is one of the hallmarks of the 21st century, with advances being made all the time. In recent years, efforts have been particularly focused on findings treatments and cures for the two greatest plagues of the past 100 years – HIV and cancer. But whereas HIV is one of the most infectious diseases to ever be observed, cancer is by far the greater killer. In 2008 alone, approximately 12.7 million cancers were diagnosed (excluding non-invasive cancers) and 7.6 million people died of cancer worldwide.

Little wonder then why so much time and energy is dedicated to ending it; and in recent years, a number of these initiatives have begun to bear fruit. One such initiative comes from the Mayo Clinic, where researchers claim they have developed a new type of software that can help classify cancerous lung nodules noninvasively, thus saving lives and health care costs.

lung-cancer-treatmentIt’s called Computer-aided Nodule Assessment and Risk Yield, or Canary, and a pilot study of the software recently appeared in the April issue of the Journal of Thoracic Oncology. According to the article, Canary uses data from high-resolution CT images of a common type of cancerous nodule in the lung and then matches them, pixel for pixel, to one of nine unique radiological exemplars. In this way, the software is able to make detailed comparisons and then determine whether or not the scans indicate the presence of cancer.

In the pilot study, Canary was able to classify lesions as either aggressive or indolent with high sensitivity, as compared to microscopic analyses of the lesions after being surgically removed and analyzed by lung pathologists. More importantly, it was able to do so without the need for internal surgery to allow a doctor to make a visual examination. This not only ensures that a patient could receive and early (and accurate) diagnosis from a simple CT scan, but also saves a great deal of money by making surgery unnecessary.

velcroAs they say, early detection is key. But where preventative medicine fails, effective treatments need to be available. And that’s where a new invention, inspired by Velcro comes into play. Created by researchers at UCLA, the process is essentially a refined method of capturing and analyzing rogue cancer cells using a Velcro-like technology that works on the nanoscale. It’s called NanoVelcro, and it can detect, isolate, and analyze single cancer cells from a patient’s blood.

Researchers have long recognized that circulating tumor cells play an important role in spreading cancer to other parts of the body. When the cells can be analyzed and identified early, they can offer clues to how the disease may progress in an individual patient, and how to best tailor a personalized cancer treatment. The UCLA team developed the NanoVelcro chip (see above) to do just that, trap individual cancer cells for analysis so that early, non-invasive diagnosis can take place.

NanoVelcro-deviceThe treatment begins with a patient’s blood being pumped in through the NanoVelcro Chip, where tiny hairs protruding from the cancer cells stick to the nanofiber structures on the device’s surface. Then, the scientists selectively cut out the cancer cells using laser microdissection and subject the isolated and purified cancer cells to single cell sequencing. This last step reveals mutations in the genetic material of the cells and may help doctors personalize therapies to the patient’s unique form of cancer.

The UCLA researchers say this technology may function as a liquid biopsy. Instead of removing tissue samples through a needle inserted into a solid tumor, the cancer cells can be analyzed directly from the blood stream, making analysis quicker and easier. They claim this is especially important in cancers like prostate, where biopsies are extremely difficult because the disease often spreads to bone, where the availability of the tissue is low. In addition, the technology lets doctors look at free-floating cancer cells earlier than they’d have access to a biopsy site.

Already, the chip is being tested in prostate cancer, according to research published in the journal Advanced Materials in late March. The process is also being tested by Swiss researchers to remove heavy metals from water, using nanomaterials to cling to and remove impurities like mercury and heavy metals. So in addition to assisting in the war on cancer, this new technology showcases the possibilities of nantechnology and the progress being made in that field.

Sources: news.cnet.com, fastcoexist.com