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

3-D Printed Cancer Cures and Diabetes Tests

future_medicineOne of the greatest benefits of additive manufacturing (aka. 3-D printing) is the way it is making everything – from finished goods to electronic devices – cheaper and more accessible. Modern medicine is also a beneficiary of this field of technology, with new tests and possibilities being produced all the time. In recent weeks, researchers have announced ways in which it might even help lead to a cure for cancer and combat one of the greatest health epidemics of the world.

When it comes to testing cancer drugs, researchers rely on the traditional two-dimensional method of seeing how they work on cancer cells within the confines of a Petri dish. If the drug works well, they move onto the next stage where they see how the drug deals with 3-D tumors in animals. If that goes well, then, finally, researchers start clinical trials on humans. But if it were possible to test these drugs in a 3-D scenario right away, time and money could be saved and effective treatments made available sooner.

petrie_dishesAnd now, thanks to a team led by Dr. Wei Sun of Philadelphia’s Drexel University, this may be possible. Using the techniques of 3-D printing and biofabrication, the research team was able to manufacture tumors by squirting out a mixture of cancerous and healthy biomaterial, dollop by dollop, and create a three-dimensional replica of a living tumor. Because of this, the field of cancer research could be revolutionized.

According to Sun, there’s just as huge a disconnect between what works in two versus three dimensions as there is between what works in animals versus humans. These disconnects are what make developing new cancer drugs so time consuming and expensive. You can’t just rely on a formula when switching to each new environment, testing takes time, results must be documented along the way, and adjustments made at every step.

3dprinted_tumorsWith Sun’s 3-D printing technology, a living tumor can be printed just as easily as cancer cells grow in a Petri dish. The machinery used is capable of printing with extraordinarily high resolution, which allows cells to be placed with incredible precision. The average cell is 20 microns, where as Sun’s system can place individual cells within two to three microns. That means Sun can print out extraordinarily specific, spheroid-shaped tumors in a multitude of different shapes and sizes.

But testing cancer drugs more easily is only one of the many uses of Sun’s technology. Since each tumor is different, there’s the possibility that the technology could be used to simulate individual patients’ cancers in the lab and see which drugs work most effectively on them. What’s more, Dr. Sun indicates that cancer testing is really just the beginning:

Doctors want to be able to print tissue, to make organ on the cheap. This kind of technology is what will make that happen. In 10 years, every lab and hospital will have a 3-D printing machine that can print living cells.

diabetes_worldwideOn another front, 3-D printing technology is offering new possibilities in the treatment of diabetes. Often referred to as a “rich man’s disease”, this condition is actually very prevalent in the developing world where nutrition is often poor and exercise habits are not always up to snuff. To make matters worse, in these parts of the world, the disease is not considered a serious health problem and proper means and facilities are not always available.

Enter the Reach, a cheap new diabetes test developed by a group of students from the Schulich School of Business at York University in Toronto. Relying on 3-D printing technology, the device is aimed at urban “slum-dwellers” who may be threatened with diabetes, but very likely haven’t been checked for it. It’s one of six finalists for this year’s Hult Prize, which challenges students to create social good enterprises.

?????????????????This year’s goal, which was set by Bill Clinton, is to reduce rates of non-communicable diseases among the urban poor. As part of their Social Enterprise Challenge, the 2014 Hult Prize is intended to address the challenge of building “a social health care enterprise that serves the needs of 25 million slum dwellers suffering from chronic diseases by 2019.” And as Dhaman Rakhra, one of the students on the York research team, put it:

We saw that diabetes is growing at the fastest rate among the slum population. It is also a disease that can be addressed, and where you can have an immediate impact. A lot of it is about a lifestyle change, if it’s detected early.

Roughly the size of a postage stamp, the Reach is similar to a home pregnancy test, in that it tests a patient’s urine. If someone’s urine has a certain level of glucose in it – indicating propensity for diabetes – the test changes color. Most importantly of all, the test can be printing out on a normal 3-D printer, making it unbelievably cheap (just two cents a pop!) The students plan to distribute the Square using the Avon business model, where local people will sell on the enterprise’s behalf.

slumsThe Schulich students, who are all undergraduates, plan to refine the idea over the summer, first spending time with a Hult accelerator in Cambridge, Massachusetts, then during a month-long pilot test at a large slum in Mumbai. If they should win the Hult Prize, they will be awarded one million dollars to further develop, refine and finance it. But as Rakhra claimed, the real fun comes in the form of bright minds coming together to come up with solutions to modern issues:

It’s exciting to really show that young people really can make a difference by creating a social enterprise that’s self-sustaining. It’s not something that many young business students really think about as a career path. But it’s definitely something we hope to influence.

The on-site manufacturing of cheap, effective drugs, prosthetics, and medical devices are undoubtedly one of the most exciting aspect of the revolution taking place with additive manufacturing. For starters, it is creating more cost effective ways to address health problems, which is a saving grace for patients and medical systems that are strapped for cash.. At the same time, it shows the potential that new technologies have to address social and economic inequality, rather than perpetuating it.

Sources: fastcodesign.com, fastcoexist.com, hultprize.org

The Future of Medicine: Elastic Superglue and DNA Clamps

nanomachineryIf there’s one thing medical science is looking to achieve, it’s ways of dealing with sickness and injuries that are less invasive. And now more than ever, researchers are looking to the natural world for solutions. Whether it is working with the bodies own components to promote healing, or using technologies that imitate living organism, the future of medicine is all about engineered-natural solutions.

Consider the elastic glue developed by associate professor Jeffrey Karp, a Canadian-born medical researcher working at Harvard University. Created for heart surgery, this medical adhesive is designed to replace sutures and staples as the principle means of sealing incisions and defects in heart tissue. But the real kicker? The glue was inspired by sticky natural secretions of slugs.

hlaa-4Officially known as hydrophobic light-activated adhesive (HLAA), the glue was developed in a collaboration between Boston Children’s Hospital, MIT, and Harvard-affiliated Brigham and Women’s Hospital. And in addition to being biocompatible and biodegradable (a major plus in surgery), it’s both water-resistant and elastic, allowing it to stretch as a beating heart expands and contracts.

All of this adds up to a medical invention that is far more user-friendly than stitches and staples, does not have to be removed, and will not cause complications. On top of all that, it won’t complicate healing by restricting the heart’s movements, and only becomes active when an ultraviolet light shines on it, so surgeons can more accurately bind the adhesive exactly where needed.

hlaa-3The technology could potentially be applied not just to congenital heart defects, but to a wide variety of organs and other body parts. In an recent interview with CBC Radio’s Quirks & Quarks, Karp explained the advantages of the glue:

Sutures and staples really are not mechanically similar to the tissues in the body, so they can induce stress on the tissue over time. This is a material that’s made from glycerol and sebacic acid, both of which exist in the body and can be readily metabolized. What happens over time is that this material will degrade. Cells will invade into it and on top of it, and ideally the hole will remain closed and the patient won’t require further operations.

In lab tests, biodegradable patches coated with HLAA were applied to holes in the hearts of live pigs. Despite the high pressure of the blood flowing through the organs, the patches maintained a leakproof seal for the 24-hour test period. HLAA is now being commercially developed by Paris-based start-up Gecko Biomedical, which hopes to have it on the market within two to three years.

dnaclampIn another recent development, scientists at the Université de Montréal have created a new DNA clamp capable of detecting the genetic mutations responsible for causing cancers, hemophilia, sickle cell anemia and other diseases. This clamp is not only able to detect mutations more efficiently than existing techniques, it could lead to more advanced screening tests and more efficient DNA-based nanomachines for targeted drug delivery.

To catch diseases at their earliest stages, researchers have begun looking into creating quick screening tests for specific genetic mutations that pose the greatest risk of developing into life-threatening illnesses. When the nucleotide sequence that makes up a DNA strand is altered, it is understood to be a mutation, which specific types of cancers can be caused by.

DNA-MicroarrayTo detect this type of mutation and others, researchers typically use molecular beacons or probes, which are DNA sequences that become fluorescent on detecting mutations in DNA strands. The team of international researchers that developed the DNA clamp state that their diagnostic nano machine allows them to more accurately differentiate between mutant and non-mutant DNA.

According to the research team, the DNA clamp is designed to recognize complementary DNA target sequences, binds with them, and form a stable triple helix structure, while fluorescing at the same time. Being able to identify single point mutations more easily this way is expected to help doctors identify different types of cancer risks and inform patients about the specific cancers they are likely to develop.

dna_cancerDiagnosing cancer at a genetic level could potentially help arrest the disease, before it even develops properly. Alexis Vallée-Bélisle, a Chemistry Professor at the Université de Montréal, explained the long-term benefits of this breakthrough in a recent interview:

Cancer is a very complex disease that is caused by many factors. However, most of these factors are written in DNA. We only envisage identifying the cancers or potential of cancer. As our understanding of the effect of mutations in various cancer will progress, early diagnosis of many forms of cancer will become more and more possible.

Currently the team has only tested the probe on artificial DNA, and plans are in the works to undertake testing on human samples. But the team also believes that the DNA clamp will have nanotechnological applications, specifically in the development of machines that can do targeted drug-delivery.

dna_nanomachineFor instance, in the future, DNA-based nanomachines could be assembled using many different small DNA sequences to create a 3D structure (like a box). When it encounters a disease marker, the box could then open up and deliver the anti-cancer drug, enabling smart drug delivery. What’s more, this new DNA clamp could prove intrinsic in that assembly process.

Professor Francesco Ricci of the University of Rome, who collaborated on the project, explained the potential in a recent interview:

The clamp switches that we have designed and optimized can recognize a DNA sequence with high precision and high affinity. This means that our clamp switches can be used, for example, as super-glue to assemble these nano machines and create a better and more precise 3D structure that can, for example, open in the presence of a disease marker and release a drug.

Hmm, glues inspired by mollusc secretions, machines made from DNA. Medical technology is looking less like technology and more like biology every day now!

Sources: cbc.ca, gizmag.com, (2)