Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Cedars-Sinai "Nano-Drug" Hits Brain Tumor Target Found in 2001

Abstract:
The system uses a unique triggering device to deliver antitumor drugs directly into brain tumor cells, unlike other drugs of its kind

Cedars-Sinai "Nano-Drug" Hits Brain Tumor Target Found in 2001

Los Angeles, CA | Posted on November 8th, 2010

Nine years ago, scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute detected a subtle shift occurring in the molecular makeup of the most aggressive type of brain tumors, glioblastoma multiforme. With further study, they found that a specific protein called laminin-411 plays a major role in a tumor's ability to build new blood vessels to support its growth and spread. But technology did not exist then to block this protein.

Now, employing new drug-engineering technology that is part of an advanced science called nanomedicine, the research team has created a "nanobioconjugate" drug that may be given by intravenous injection and carried in the blood to target the brain tumor. It is engineered to specifically permeate the tumor cell wall, entering endosomes, mobile compartments within cells.

As endosomes mature, they grow acidic (low pH), and a chemical component of the drug triggers at this point, breaking the endosomes' membranes. Freed drugs block the tumor cell's production of laminin-411, the "malignant" protein of new tumor vessels. By its nature, the drug is nontoxic to non-tumor cells; side effects associated with conventional chemotherapy are not an issue with this class of drugs.

This approach is believed to be the first of its kind - the first application of a pH-dependent endosome escape unit in drugs administered intravenously for brain cancer treatment - as reported in Proceedings of the National Academy of Sciences (online). Studies in lab mice show this system allows large amounts of antitumor drug to accumulate in tumors, significantly slowing the growth of new vessels and the tumors themselves. Tumors in animals treated with the drug were 90 percent smaller than those in a control group.

Gliomas, a type of malignant brain tumors, are extremely difficult to treat. Their tendency to spread into healthy brain tissue and their ability to reappear in distant locations make them virtually impossible to surgically remove completely. They resist chemotherapy and radiation therapy, and the brain itself is "protected" by the blood-brain barrier and immune system mechanisms that thwart most therapies.

The system developed at Cedars-Sinai - a nanobioconjugate - appears to clear major hurdles to brain tumor drug treatment. Nanoconjugates are the latest evolution of molecular drugs designed to enter cells and specifically alter defined targets within them. As suggested by the term "bioconjugate," these systems contain chemical "modules" attached (conjugated) to a delivery vehicle by strong chemical bonds. Such bonds prevent the components from being damaged or separated in tissues or blood plasma during transit. But with inventive drug engineering, the antitumor component activates directly inside tumor cells.

A nanoconjugate exists as a single chemical unit, with its components performing critical tasks in a predetermined sequence and attacking several targets simultaneously. The ultimate assault on a tumor cell depends on a complex, well-choreographed chain of biochemical events, such as: penetrating the blood-brain barrier and the blood-brain tumor barrier; specifically homing to tumor cells; permeating the walls of blood vessels and tumor cells; releasing antitumor drugs at the right place and time; and dismantling mechanisms that help tumor-feeding blood vessels grow.

"This nanobioconjugate is different from earlier nanomedicine drugs because it delivers and releases antitumor drugs within tumor cells, not just at the site of a tumor," said research scientist Julia Y. Ljubimova, M.D., Ph.D., senior author of the article. She directs the Drug Delivery and Nanomedicine Laboratory in the Department of Neurosurgery at Cedars-Sinai. Other major contributors to this study and the article include: Hui Ding, Ph.D., and Eggehard Holler, Ph.D., chemists, biochemists and immunologists. Holler is affiliated with both Cedars-Sinai and the University of Regensburg in Germany.

Cedars-Sinai's drug, a macromolecule of 20 to 30 nanometers in size, is based on a highly purified form of polymalic acid derived from the single cell organism Physarum polycephalum. When the nanoconjugate has accomplished its tasks, the body digests it completely, leaving no harmful residue.

"Based on our studies, this nanoconjugate appears to be a safe and efficient delivery platform that also may be appropriate in the treatment of degenerative brain conditions and a wide array of other disorders. It is harmlessly degraded to carbon dioxide and water, nontoxic to normal tissue, and, unlike some drugs, it is non-immunogenic, meaning that it does not stimulate the immune system to the point of causing allergic reactions that can range from mild coughs or rashes to sudden, life-threatening symptoms," Ljubimova said. Researchers anticipate that human clinical trials of the drug will begin in the near future.

The National Cancer Institute announced in September that, as part of its Nanotechnology in Cancer Program, Cedars-Sinai's nanomedicine research laboratory will receive a five-year grant for more study on its nanoconjugate. As a Cancer Nanotechnology Platform Partner, Cedars-Sinai is recognized for dedication "to the advancement of new nanotechnology discoveries and their transformation into cancer-relevant applications with clinical utility."

Ljubimova's lab is part of Cedars-Sinai's Maxine Dunitz Neurosurgical Institute, directed by Keith L. Black, M.D., chairman of the Department of Neurosurgery. He is a researcher and author of this paper. With neurosurgeons, chemists, cancer specialists and other experts conducting research at a single site, Cedars-Sinai teams have made many significant discoveries and gained respect typically reserved for large centers with many scientists on sprawling campuses.

Black, Ljubimova and Holler have equity interest in Arrogene, a company with interest in this technology. The current study was supported by funding from the National Institutes of Health/National Cancer Institute, the Winnick Family Foundation, and the Department of Neurosurgery at Cedars-Sinai Medical Center.

Citation: Proceedings of the National Academy of Sciences: "Inhibition of brain tumor growth by intravenous polymalic acid nanobioconjugate with pH-dependent drug release."

####

For more information, please click here

Copyright © Cedars-Sinai

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

Self-assembling biomaterial forms nanostructure templates for human tissue formation April 27th, 2015

International research team discovers new mechanism behind malaria progression: Findings provide a new avenue for research in malaria treatment April 27th, 2015

More is less in novel electronic material: Adding electrons actually shrinks the system April 27th, 2015

Sensor Designed in Iran Able to Remove Formaldehyde Gas from Environment April 27th, 2015

Possible Futures

Printing Silicon on Paper, with Lasers April 21st, 2015

A glass fiber that brings light to a standstill: By coupling photons to atoms, light in a glass fiber can be slowed down to the speed of an express train; for a short while it can even be brought to a complete stop April 9th, 2015

Nanotechnology in Medical Devices Market is expected to reach $8.5 Billion by 2019 March 25th, 2015

Nanotechnology Enabled Drug Delivery to Influence Future Diagnosis and Treatments of Diseases March 21st, 2015

Academic/Education

SEFCU, SUNY Poly CNSE Announce Winning Student-Led Teams in the 6th Annual $500,000 New York Business Plan Competition April 25th, 2015

Iranian Female Professor Awarded UNESCO Medal in Nanoscience April 20th, 2015

JPK reports on the use of the NanoWizardŽ 3 AFM system at the Hebrew University of Jerusalem April 14th, 2015

UK National Graphene Institute Selects Bruker as Official Partner: World-Leading Graphene Research Facility Purchases Multiple Bruker AFMs April 7th, 2015

Nanomedicine

Self-assembling biomaterial forms nanostructure templates for human tissue formation April 27th, 2015

International research team discovers new mechanism behind malaria progression: Findings provide a new avenue for research in malaria treatment April 27th, 2015

Scientists join forces to reveal the mass and shape of single molecules April 27th, 2015

Northwestern scientists develop first liquid nanolaser: Technology could lead to new way of doing 'lab on a chip' medical diagnostics April 25th, 2015

Announcements

Scientists join forces to reveal the mass and shape of single molecules April 27th, 2015

The 16th Trends in Nanotechnology International Conference (TNT 2015) unveils 25 Keynote Speakers: Call for abstracts open April 27th, 2015

Graphenea celebrates fifth anniversary April 27th, 2015

Sensor Designed in Iran Able to Remove Formaldehyde Gas from Environment April 27th, 2015

Nanobiotechnology

Self-assembling biomaterial forms nanostructure templates for human tissue formation April 27th, 2015

Scientists join forces to reveal the mass and shape of single molecules April 27th, 2015

A silver lining: UCSB researchers cradle silver nanoclusters inside synthetic DNA to create a programmed, tunable fluorescent array April 23rd, 2015

Scientists Use Nanoscale Building Blocks and DNA 'Glue' to Shape 3D Superlattices: New approach to designing ordered composite materials for possible energy applications April 23rd, 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