Nanotechnology Now

Our NanoNews Digest Sponsors



Heifer International

Wikipedia Affiliate Button


android tablet pc

Home > Press > Novel Nanoparticles Shown to Inhibit Ewing’s Sarcoma

Abstract:
"Trojan horse" approach shown to inhibit Ewing’s sarcoma in an animal model

Novel Gene-silencing Nanoparticles Shown to Inhibit Ewing’s Sarcoma

Anaheim, CA | April 19, 2005

A novel delivery system that transports gene silencing nanoparticles into tumor cells has been shown to inhibit Ewing’s sarcoma in an animal model of the disease.

In this classic “Trojan horse” approach, a protein called transferrin that normally delivers iron into cells is modified to also smuggle into tumor cells siRNA (short interfering RNA) encased in nano-sized sugar polymers. The siRNA was designed to target a specific growth-promoting gene called EWS-FLI1 that’s active only in Ewing’s sarcoma tumors.

Once inside these cells, the genetic machinery of the tumor cells are effectively silenced or shut down, preventing further growth.

“This is the first study to show that systemic administration of siRNA can inhibit disseminated tumor growth,” said Siwen Hu, a postdoctoral fellow at Children’s Hospital of Los Angeles and the University of Southern California, and one of the study’s lead investigators.

“We conclude that this novel delivery system is a powerful and simple method to induce gene silencing, with the potential to move to clinical trials,” said Hu, who presented the results at the 96th Annual Meeting of the American Association for Cancer Research.

In recent years, scientists have been intrigued by the potential of siRNA to block the activity of genes that promote the growth of tumors. Harnessing the power of this new technology, however, has proved daunting for a variety of reasons, including the ability to deliver these bits of genetic material in high concentrations to specific tumor sites, while avoiding degradation.

To overcome these hurdles, the scientists employed a sugar-containing polymer invented by chemical engineers at the California Institute of Technology. For this experiment, the polymer binds to and condenses the engineered siRNA into nanoparticles that, in effect, form a protective shield around their precious genetic cargo. These nanoparticles, in turn, are attached to transferrin, a protein that typically carries iron molecules through the bloodstream until it meets up with a transferrin receptor on the surface of another cell. The transferrin binds tightly to a receptor on the cell’s surface, where it is drawn inside and surrounded by a small vesicle. The vessels are acidified, causing the nanoparticles to release its contents – the siRNA.

“Since transferrin receptors are upregulated in tumor cells, this delivery system will home in on tumor cells, leaving normal cells in tact,” Hu said.

To test their new delivery system, the scientists targeted tumor cells from the patients of Ewing’s sarcoma, a rare and often deadly bone cancer that generally strikes young adults. Despite aggressive therapy, about 40 percent of patients with Ewing’s family tumors and 95 percent with metastases die as a result of their disease.

Scientists now recognize that Ewing’s sarcoma results when two chromosomes break and trade their genetic content in what’s technically called a “translocation,” activating the oncogene EWS-FLI1 which triggers the tumor growth characteristic for this cancer.

In their experiment, siRNA was delivered to this growth-promoting region of the tumor cell, effectively reducing cell replication by 80 percent.

The scientists then tried their novel technology in laboratory mice grafted with human Ewing’s sarcoma tumors. Following three consecutive days of treatment, the scientists observed strong, but transient, inhibition of tumor growth.

However, when used over longer durations (twice-weekly injections up to four weeks), the results were striking.

“Long-term treatments with this delivery system markedly inhibited tumor growth, with little or no tumor growth in many animals,” said Hu.

Future experiments will combine the novel delivery system with small molecular anti-tumor agents, with hopes of creating a new and effective way to treat Ewing’s sarcoma and other tumors in the clinic.

“Clinically, Ewing’s patients are treated with combination of chemotherapeutic agents, but despite aggressive treatments, the patient outcomes are poor,” said Hu.

“The delivery system we’re developing can shield the drugs from degradation before reaching the target sites, while delivering siRNA for more specificity and potency so as to lower the required dose for efficacy.”

The study was a collaborative effort between the laboratory of Timothy J. Triche, at Children’s Hospital of Los Angeles; and the laboratory of Mark E. Davis, at Caltech. Also participating in the study were Jeremy D. Heidel and Derek W. Barlett, both at Caltech.

Support for this research came from the Las Madrinas endowment in Molecular Genetics and Molecular Pathology at the Children’s Hospital of Los Angeles, the Whitaker Foundation, with the National Science Foundation funding part of the work at Caltech.

####


About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.



Contact:
Warren Froelich/AACR
215/440-9300
froelich@aacr.org

Kellie Hanzak/Spectrum Science
202/955-6222
kellie@spectrumscience.com
In Anaheim: (4/16-4/20)
Anaheim Convention Center
(714) 765-2030


Copyright © American Association for Cancer Research

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

Possible Futures

Air Force’s 30-year plan seeks 'strategic agility' August 1st, 2014

IBM Announces $3 Billion Research Initiative to Tackle Chip Grand Challenges for Cloud and Big Data Systems: Scientists and engineers to push limits of silicon technology to 7 nanometers and below and create post-silicon future July 10th, 2014

Virus structure inspires novel understanding of onion-like carbon nanoparticles April 10th, 2014

Local girl does good March 22nd, 2014

Nanomedicine

Treatment of Cell Infection by Nanotechnology September 15th, 2014

Researchers Create World’s Largest DNA Origami September 11th, 2014

Iranian Scientists Discover Nanotechnology Method to Remove Limitations in Tumor Surgery September 11th, 2014

Iranian Nanotechnology Scientists Produce Polymeric Scaffolds for Tissue Engineering September 11th, 2014

Announcements

Effective Nanotechnology Innovations to Receive Mustafa Prize September 16th, 2014

‘Small’ transformation yields big changes September 16th, 2014

Rice rolls 'neat' nanotube fibers: Rice University researchers' acid-free approach leads to strong conductive carbon threads September 15th, 2014

Simple, Cost-Effective Method Proposed for Synthesizing Zinc Oxide Nanopigments September 15th, 2014

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







© Copyright 1999-2014 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE