Navigation Links
New nanomedicine resolves inflammation, promotes tissue healing
Date:3/19/2013

NEW YORK, NY (March 18, 2013) A multicenter team of researchers, including scientists at Columbia University Medical Center (CUMC), Brigham and Women's Hospital (BWH), Mount Sinai School of Medicine, and Massachusetts Institute of Technology, has developed biodegradable nanoparticles that are capable of delivering inflammation-resolving drugs to sites of tissue injury. The nanoparticles, which were successfully tested in mice, have potential for the treatment of a wide array of diseases characterized by excessive inflammation, such as atherosclerosis. The study was published today in the online edition of the Proceedings of the National Academy of Sciences.

A key way in which the body protects itself against infection or injury is through acute inflammation. Ideally, this response first promotes the clearance of pathogens or damaged tissue; then, through a process called inflammation resolution, it clears cellular debris and inflammatory mediators and restores the tissue to its normal state. However, in many conditions, including heart disease, arthritis, and neurodegenerative diseases, the inflammatory process never resolves, leading to tissue damage.

"A variety of medications can be used to control inflammation. Such treatments, however, usually have significant side effects and dampen the positive aspects of the inflammatory response," said co-senior author Ira Tabas, MD, PhD, the Richard J. Stock Professor, Department of Medicine, and professor of Pathology & Cell Biology (in Physiology and Cellular Biophysics) at CUMC. The other co-senior author is Omid Farokhzad, MD, Associate Professor of Anesthesiology and Director of Laboratory of Nanomedicine and Biomaterials at Brigham and Women's Hospital (BWH).

To overcome these obstacles, the researchers incorporated two advances. First, based on an idea from co-lead author Gabrielle Fredman, PhD, a postdoctoral fellow at CUMC, they took advantage of a 24-amino-acid peptide, Ac2-26, which is derived from a naturally occurring protein mediator of inflammation resolution called annexin A1. Second, rather than simply inject the "naked" peptide into injured mice, they packaged the peptide into nanoparticles, designed by the BWH group, that are able to target drugs to sites of tissue injury. The nanoparticles were given this ability through the addition of two components: one that gives them stealthlike properties, enabling them to avoid detection and clearance by white blood cells and the liver; and a second that gives them the ability to target collagen IV, a protein found at sites of tissue injury.

Each nanoparticle is less than 100 nanometers in diameter, or 1/100,000th the diameter of a human hair.

The nanoparticles were tested in mice with peritonitis (inflammation of the peritoneum, the thin tissue that lines the inner wall of the abdomen) or hind-limb ischemia-reperfusion injury (tissue damage caused when blood supply returns to tissue after a period of ischemia, or lack of oxygen). In the mice with peritonitis, intravenous administration of the Ac2-26-containing nanoparticles was significantly more effective at limiting recruitment of neutrophils (a type of inflammatory white blood cell) and at increasing the resolution of inflammation than was intravenous administration of naked Ac2-26. In mice with reperfusion injury, the nanoparticles reduced tissue damage in comparison with either of two types of control nanoparticles: those with a peptide in which the 24 amino acids were scrambled to render it biologically inactive and Ac2-26 nanoparticles without the collagen IV-targeting component.

"These targeted polymeric nanoparticles are capable at very small doses of stopping neutrophils, the most abundant form of white blood cells, from infiltrating sites of disease or injury," said co-lead author Nazila Kamaly, PhD, a postdoctoral fellow at BWH. "This action stops the neutrophils from secreting further signaling molecules that can lead to a constant hyper-inflammatory state and further disease complications."

"The beauty of this approach is that, unlike many other anti-inflammatory approaches, it takes advantage of nature's own design for preventing inflammation-induced damage, which does not compromise host defense and promotes tissue repair," said Dr. Tabas.

While the nanoparticles do spread to tissues throughout the body, they tend to concentrate in areas of inflammation. "In theory, this should allow physicians to use smaller-than-usual doses of medications and reduce unwanted side effects," said Dr. Fredman.

The team is currently designing nanoparticles for the treatment of atherosclerosis. Preliminary studies show that the nanoparticles are capable of targeting atherosclerotic plaques.

The authors have filed a patent for targeted polymeric inflammation-resolving nanoparticles to treat a variety of chronic inflammatory diseases, including atherosclerosis, autoimmune disease, type 2 diabetes, and Alzheimer's disease.


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

Related biology technology :

1. First targeted and programmable nanomedicine to show clinical antitumor effects published
2. Researchers pioneer worlds first HIV/AIDS nanomedicines
3. Clearing up inflammation with pro-resolving nanomedicines
4. Zyngenia, Inc. Promotes Chief Scientific Officer and Hires Chief Business Officer
5. Inovio Pharmaceuticals Promotes Niranjan Sardesai to Chief Operating Officer
6. BioSpace Promotes the Northeast Corridors Life Science Industry
7. Intellitech Announces New Micro Pump Promotes Rapid Growth of Emerging BioTech
8. New Mobile Solution from FreshLoc Promotes Safety and Prevents Non Compliance
9. AMRI Promotes Takeshi Yura, Ph.D., to Vice President of Discovery and Development Services, Asia
10. New method for producing precursor of neurons, bone and other important tissues from stem cells
11. BioStorage Technologies Partners with Susan G. Komen for the Cure Tissue Bank at IU Simon Cancer Center to Raise Money and Awareness for Breast Cancer Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... DIEGO , June 24, 2016 ... more sensitively detects cancers susceptible to PARP inhibitors ... circulating tumor cells (CTCs). The new test has ... HRD-targeted therapeutics in multiple cancer types. ... targeting DNA damage response pathways, including PARP, ATM, ...
(Date:6/23/2016)... Mass. , June 23, 2016   ... development of novel compounds designed to target cancer ... napabucasin, has been granted Orphan Drug Designation from ... the treatment of gastric cancer, including gastroesophageal junction ... stemness inhibitor designed to inhibit cancer stemness pathways ...
(Date:6/23/2016)... June 23, 2016  The Prostate Cancer Foundation (PCF) is pleased ... and faster cures for prostate cancer. Members of the Class of 2016 were ... Read More About the Class of 2016 PCF Young ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case ... Denmark detail how a patient who developed lymphedema after being treated for breast cancer ... could change the paradigm for dealing with this debilitating, frequent side effect of cancer ...
Breaking Biology Technology:
(Date:6/15/2016)... , June 15, 2016 ... report titled "Gesture Recognition Market by Application Market - Global Industry ... - 2024". According to the report, the  global gesture ... in 2015 and is estimated to grow at ... billion by 2024.  Increasing application of ...
(Date:6/2/2016)... The Department of Transport Management (DOTM) of ... Dollar project, for the , Supply and Delivery ... IT Infrastructure , to Decatur ... Identity Management Solutions. Numerous renowned international vendors participated in the ... was selected for the most compliant and innovative solution. The ...
(Date:5/20/2016)... May 20, 2016  VoiceIt is excited to ... VoicePass. By working together, VoiceIt and ... VoiceIt and VoicePass take slightly different approaches to ... both security and usability. ... this new partnership. "This marketing and ...
Breaking Biology News(10 mins):