Navigation Links
UGA researchers boost efficacy of drugs by using nanoparticles to target 'powerhouse of cells'
Date:9/19/2012

Athens, Ga. - Nanoparticles have shown great promise in the targeted delivery of drugs to cells, but researchers at the University of Georgia have refined the drug delivery process further by using nanoparticles to deliver drugs to a specific organelle within cells.

By targeting mitochondria, often called "the powerhouse of cells," the researchers increased the effectiveness of mitochondria-acting therapeutics used to treat cancer, Alzheimer's disease and obesity in studies conducted with cultured cells.

"The mitochondrion is a complex organelle that is very difficult to reach, but these nanoparticles are engineered so that they do the right job in the right place," said senior author Shanta Dhar, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences.

Dhar and her co-author, doctoral student Sean Marrache, used a biodegradable, FDA-approved polymer to fabricate their nanoparticles and then used the particles to encapsulate and test drugs that treat a variety of conditions. Their results were published this week in early edition of the journal Proceedings of the National Academy of Sciences.

To test the effectiveness of their drug targeting system against cancer, they encapsulated the drug lonidamine, which works by inhibiting energy production in the mitochondria, and, separately, a form of the antioxidant vitamin E. They then treated cultured cancer cells and found that mitochondrial targeting increased the effectiveness of the drugs by more than 100 times when compared to the drugs alone and by five times when compared to the delivery of drugs with nanoparticles that target the outside of cells.

Similarly, the compound curcumin has shown promise in inhibiting formation of the amyloid plaques that are a hallmark of Alzheimer's disease, but it quickly degrades in the presence of light and is broken down rapidly by the body. By encapsulating curcumin in the mitochondria-targeting nanoparticles, however, the researchers were able to restore the ability of brain cells in culture to survive despite the presence of a compound that encourages plaque formation. Nearly 100 percent of the cells treated with the mitochondria-targeting nanoparticles survived in the presence of the plaque-inducing compound, compared to 67 percent of cells treated with free curcumin and 70 percent of cells treated with nanoparticles that target the outside of cells.

Finally, the researchers encapsulated the obesity drug 2,4-DNPwhich works by making energy production in the mitochondria less efficientin their nanoparticles and found that it reduced the production of fat by cultured cells known as preadipocytes by 67 percent compared to cells treated with the drug alone and by 61 percent of cells treated with nanoparticles that target the outside of cells.

"A lot of diseases are associated with dysfunctional mitochondria, but many of the drugs that act on the mitochondria can't get there," Marrache said. "Rather than try to alter the drugs, which can reduce their effectiveness, we encapsulate them in these nanoparticles and precisely deliver them to the mitochondria."

Dhar said that getting drugs to the mitochondria is no simple feat. Upon entering cells, nanoparticles enter a sorting center known as the endosome. The first thing Dhar and Marrache had to demonstrate was that the nanoparticles escape from the endosome and don't end up in the cells' disposal center, the lysosome.

The mitochondria itself is protected by two membranes separated by an interstitial space. The outer membrane only permits molecules of a certain size to pass through, while the inner membrane only permits molecules of a given range of charges to pass. The researchers constructed a library of nanoparticles and tested them until they identified the optimum size range64 to 80 nanometers, or approximately 1,000 times finer than the width of a human hairand an optimum surface charge, plus 34 millivolts.

Dhar notes the components they used to create the nanoparticles are FDA approved and that their methods are highly reproducible and therefore have the potential to be translated into clinical settings. The researchers are currently testing their targeted delivery system in rodents and say that preliminary results are promising.

"Mitochondrial dysfunctions cause many disorders in humans," Dhar said, " so there are several potential applications for this delivery system."


'/>"/>

Contact: Shanta Dhar
shanta@uga.edu
706-542-1012
University of Georgia
Source:Eurekalert  

Related medicine news :

1. NIH awards $20 million over 5 years to train next generation of global health researchers
2. Researchers develop a new cell and animal model of inflammatory breast cancer
3. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
4. Researchers Find Gene Mutations That May Be a Key to Autism
5. Researchers find evidence of banned antibiotics in poultry products
6. NJ stroke researchers report advances in spatial neglect research at AAN Conference
7. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
8. Researchers Map Brain Regions Linked to Intelligence
9. Researchers ID Genes That May Determine Mental Illness
10. Researchers Develop Blood Test for Depression
11. University of Cincinnati researchers win $3.7M grant from US Department of Defense
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UGA researchers boost efficacy of drugs by using nanoparticles to target 'powerhouse of cells'
(Date:6/25/2016)... ... June 25, 2016 , ... ... issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the ... several important health care topics including advance care planning, healthcare costs and patient ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/24/2016)... ... ... Those who have experienced traumatic events may suffer from a complex set of ... or alcohol abuse, as a coping mechanism. To avoid this pain and suffering, Serenity ... event. , Trauma sufferers tend to feel a range of emotions, from depression, guilt, ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... now offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with ... Damon brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty Network, ... M. Weintraub as a prominent plastic surgeon and the network’s newest partner. ... the most handsome men, look naturally attractive. Plastic surgery should be invisible.” He ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016  Global Blood Therapeutics, Inc. (GBT) (NASDAQ: ... novel therapeutics for the treatment of grievous blood-based ... closing of its previously announced underwritten public offering ... public offering price of $18.75 per share. All ... by GBT. GBT estimates net proceeds from the ...
(Date:6/24/2016)... , June 24, 2016 ... has announced the addition of the " Global ... This report ... provides an updated review, including its applications in various ... total market, which includes three main industries: pharmaceutical and ...
(Date:6/24/2016)... 2016 The Academy of Managed Care Pharmacy ... that would allow biopharmaceutical companies to more easily share ... formulary and coverage decisions, a move that addresses the ... The recommendations address restrictions in the sharing ... drug label, a prohibition that hinders decision makers from ...
Breaking Medicine Technology: