Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Targeting Cancer with a Triple Threat

Published: Tuesday, April 15, 2014
Last Updated: Tuesday, April 15, 2014
Bookmark and Share
MIT chemists design nanoparticles that can deliver three cancer drugs at a time.

Delivering chemotherapy drugs in nanoparticle form could help reduce side effects by targeting the drugs directly to the tumors. In recent years, scientists have developed nanoparticles that deliver one or two chemotherapy drugs, but it has been difficult to design particles that can carry any more than that in a precise ratio.

Now MIT chemists have devised a new way to build such nanoparticles, making it much easier to include three or more different drugs. In a paper published in the Journal of the American Chemical Society, the researchers showed that they could load their particles with three drugs commonly used to treat ovarian cancer.

“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,” says Jeremiah Johnson, an assistant professor of chemistry at MIT and the senior author of the new paper.

Such particles could be designed to carry even more drugs, allowing researchers to develop new treatment regimens that could better kill cancer cells while avoiding the side effects of traditional chemotherapy. In the JACS paper, Johnson and colleagues demonstrated that the triple-threat nanoparticles could kill ovarian cancer cells more effectively than particles carrying only one or two drugs, and they have begun testing the particles against tumors in animals.

Longyan Liao, a postdoc in Johnson’s lab, is the paper’s lead author.

Putting the pieces together

Johnson’s new approach overcomes the inherent limitations of the two methods most often used to produce drug-delivering nanoparticles: encapsulating small drug molecules inside the particles or chemically attaching them to the particle. With both of these techniques, the reactions required to assemble the particles become increasingly difficult with each new drug that is added.

Combining these two approaches — encapsulating one drug inside a particle and attaching a different one to the surface — has had some success, but is still limited to two drugs.

Johnson set out to create a new type of particle that would overcome those constraints, enabling the loading of any number of different drugs. Instead of building the particle and then attaching drug molecules, he created building blocks that already include the drug. These building blocks can be joined together in a very specific structure, and the researchers can precisely control how much of each drug is included.

Each building block consists of three components: the drug molecule, a linking unit that can connect to other blocks, and a chain of polyethylene glycol (PEG), which helps protect the particle from being broken down in the body. Hundreds of these blocks can be linked using an approach Johnson developed, called “brush first polymerization.”

“This is a new way to build the particles from the beginning,” Johnson says. “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.”

Varying combinations

For this paper, the researchers created particles that carry the drugs cisplatin, doxorubicin, and camptothecin, which are often used alone or in combination to treat ovarian cancer.

Each particle carries the three drugs in a specific ratio that matches the maximum tolerated dose of each drug, and each drug has its own release mechanism. Cisplatin is freed as soon as the particle enters a cell, as the bonds holding it to the particle break down on exposure to glutathione, an antioxidant present in cells. Camptothecin is also released quickly when it encounters cellular enzymes called esterases.

The third drug, doxorubicin, was designed so that it would be released only when ultraviolet light shines on the particle. Once all three drugs are released, all that is left behind is PEG, which is easily biodegradable.

Working with researchers in the lab of Paula Hammond, the David H. Koch Professor of Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research, the team tested the particles against ovarian cancer cells grown in the lab. Particles carrying all three drugs killed the cancer cells at a higher rate than those that delivered only one or two drugs.

Johnson’s lab is now working on particles that carry four drugs, and the researchers are also planning to tag the particles with molecules that will allow them to home to tumor cells by interacting with proteins found on the cell surfaces.

Johnson also envisions that the ability to reliably produce large quantities of multidrug-carrying nanoparticles will enable large-scale testing of possible new cancer treatments. “It’s important to be able to rapidly and efficiently make particles with different ratios of multiple drugs, so that you can test them for their activity,” he says. “We can’t just make one particle, we need to be able to make different ratios, which our method can easily do.”

Other authors of the paper are graduate students Jenny Liu and Stephen Morton, and postdocs Erik Dreaden and Kevin Shopsowitz.

The research was funded by the MIT Research Support Committee, the Department of Defense Ovarian Cancer Research Program Teal Innovator Award, the National Institutes of Health, the National Sciences and Engineering Research Council, and the Koch Institute Support Grant from the National Cancer Institute.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Thursday, August 27, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Friday, July 31, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Nanoparticles Can Clean Up Environmental Pollutants
Researchers have found that nanomaterials and UV light can “trap” chemicals for easy removal from soil and water.
Thursday, July 23, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Longstanding Problem Put to Rest
Proof that a 40-year-old algorithm for comparing genomes is the best possible will come as a relief to computer scientists.
Thursday, June 11, 2015
Diagnosing Cancer with Help from Bacteria
Engineered probiotics can detect tumors in the liver.
Friday, May 29, 2015
Master Gene Regulator Could Be New Target For Schizophrenia Treatment
Researchers at MIT’s Picower Institute for Learning and Memory have identified a master genetic regulator that could account for faulty brain functions that contribute to schizophrenia.
Wednesday, May 27, 2015
Brain Tumor Weakness Identified
Discovery could offer a new target for treatment of glioblastoma.
Thursday, April 09, 2015
New Nanodevice Defeats Drug Resistance
Tiny particles embedded in gel can turn off drug-resistance genes, then release cancer drugs.
Wednesday, March 04, 2015
New Nanodevice Defeats Drug Resistance
Tiny particles embedded in gel can turn off drug-resistance genes, then release cancer drugs.
Tuesday, March 03, 2015
Scientific News
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Five New Genetic Variants Linked to Brain Cancer Identified
The biggest ever study of DNA from people with glioma – the most common form of brain cancer – has discovered five new genetic variants associated with the disease.
Predictive Model for Breast Cancer Progression
Biomedical engineers have demonstrated a proof-of-principle technique that could give women and their oncologists more personalized information to help them choose options for treating breast cancer.
Fatty Liver Disease and Scarring Have Strong Genetic Component
Researchers say that hepatic fibrosis, which involves scarring of the liver that can result in dysfunction and, in severe cases, cirrhosis and cancer, may be as much a consequence of genetics as environmental factors.
Specific Variations in RNA Splicing Linked to Breast Cancer
Researchers have identified cellular changes that may play a role in converting normal breast cells into tumors. Targeting these changes could potentially lead to therapies for some forms of breast cancer.
Finding Links and Missing Genes
A catalogue of large-scale genetic changes around the world.
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Gene Expression: A Snapshot of Stem Cell Development
New genes found that regulate development of stem cells.
Assessing Cancer Patient Survival and Drug Sensitivity
RNA editing events another way to investigate biomarkers and therapy targets.
A Natural History of Neurons
Diverse mutations reveal lineage of brain cells.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos