Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Chemotherapy timing is key to success: Nanoparticles that stagger delivery of two drugs knock out aggressive tumors in mice.

The nanoparticle contains the cancer drug doxorubicin (green spheres) in its core. Erlotinib is embedded in the red outer shell. Attached to the surface are chains of polyethylene glycol (PEG), in yellow.

Image: Stephen Morton
The nanoparticle contains the cancer drug doxorubicin (green spheres) in its core. Erlotinib is embedded in the red outer shell. Attached to the surface are chains of polyethylene glycol (PEG), in yellow.

Image: Stephen Morton

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.

Chemotherapy 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

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."

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

####

For more information, please click here

Contacts:
Andrew Carleen
MIT News Office

T: 617-253-1682

Copyright © Massachusetts Institute of Technology

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

'Microcombing' creates stronger, more conductive carbon nanotube films May 5th, 2015

Testing Facility for Graphene Enhanced Composite Pipes May 5th, 2015

Arrowhead Completes Dosing Healthy Volunteers and Initiates Transition to Patients in Phase 1 Study of ARC-AAT May 5th, 2015

Silicon Storage Technology and GLOBALFOUNDRIES Announce Qualification of Automotive Grade 55nm Embedded Flash Memory Technology May 5th, 2015

Govt.-Legislation/Regulation/Funding/Policy

New chip architecture may provide foundation for quantum computer: Researchers at the Georgia Tech Research Institute have developed a microfabricated ion trap architecture that holds promise for increasing the density of qubits in future quantum computers May 5th, 2015

'Microcombing' creates stronger, more conductive carbon nanotube films May 5th, 2015

Defects in atomically thin semiconductor emit single photons: Researchers create optically active quantum dots in 2-D semiconductor for the first time; may have applications for integrated photonics May 4th, 2015

From brittle to plastic in 1 breath: Rice University theorists show environments can alter 2-D materials' basic properties May 4th, 2015

Nanomedicine

Arrowhead Completes Dosing Healthy Volunteers and Initiates Transition to Patients in Phase 1 Study of ARC-AAT May 5th, 2015

Arrowhead to Report Fiscal 2015 Second Quarter Financial Results May 4th, 2015

New Nanodrug Produced in Iran from Milk Thistle May 4th, 2015

Antibacterial Ceramic Nanoparticles, Appropriate Material for Medical Devices May 3rd, 2015

Discoveries

Improving organic transistors that drive flexible and conformable electronics: UMass Amherst scientists advance understanding of strain effects on performance May 5th, 2015

New chip architecture may provide foundation for quantum computer: Researchers at the Georgia Tech Research Institute have developed a microfabricated ion trap architecture that holds promise for increasing the density of qubits in future quantum computers May 5th, 2015

'Microcombing' creates stronger, more conductive carbon nanotube films May 5th, 2015

Iranian Scientists Present Model to Study Mechanical Vibrations of Structures Containing Nanocomposites May 5th, 2015

Announcements

'Microcombing' creates stronger, more conductive carbon nanotube films May 5th, 2015

Testing Facility for Graphene Enhanced Composite Pipes May 5th, 2015

Arrowhead Completes Dosing Healthy Volunteers and Initiates Transition to Patients in Phase 1 Study of ARC-AAT May 5th, 2015

Silicon Storage Technology and GLOBALFOUNDRIES Announce Qualification of Automotive Grade 55nm Embedded Flash Memory Technology May 5th, 2015

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

Improving organic transistors that drive flexible and conformable electronics: UMass Amherst scientists advance understanding of strain effects on performance May 5th, 2015

New chip architecture may provide foundation for quantum computer: Researchers at the Georgia Tech Research Institute have developed a microfabricated ion trap architecture that holds promise for increasing the density of qubits in future quantum computers May 5th, 2015

'Microcombing' creates stronger, more conductive carbon nanotube films May 5th, 2015

Iranian Scientists Present Model to Study Mechanical Vibrations of Structures Containing Nanocomposites May 5th, 2015

Nanobiotechnology

Artificial photosynthesis could help make fuels, plastics and medicine April 29th, 2015

A phone with the ultimate macro feature: New attachment turns a smartphone into a microscope that can image and size DNA molecules 50,000 times thinner than a human hair April 29th, 2015

An effective, biodegradable and broad-spectrum nanoparticles as potent antibacterial agents April 28th, 2015

Weighing -- and imaging -- molecules one at a time April 28th, 2015

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project