Nanoparticles will increase the effectiveness of drugs against cancer, Alzheimer's disease and obesity
Researchers from the University of Georgia – associate professor Shanta Dhar and her graduate student Sean Marrache – have developed a method of using nanoparticles to deliver drugs inside the cell, directly into the mitochondria. In experiments on cell cultures, this approach significantly increased the effectiveness of drugs acting on mitochondria used in the treatment of cancer, Alzheimer's disease and obesity.
The authors manufactured nanoparticles from a biodegradable polymer approved by the U.S. Food and Drug Administration for medical use, and used them to encapsulate several drugs. The effectiveness of the resulting complexes was tested on cellular models of various diseases.
The mitochondria has two membranes separated by an interstitial space. The outer membrane passes only molecules of a certain size, whereas the inner membrane only passes molecules carrying a certain electric charge.
To overcome this double barrier, scientists created a library of nanoparticles and tested them until they determined the optimal size range for penetration into mitochondria (64-80 nanometers) and the optimal surface charge: +34 millivolts.
To evaluate the effectiveness of the developed system against malignant cells, the drug lonidamine, which suppresses the production of energy in mitochondria, and also, separately, one of the forms of vitamin E, which has an antioxidant effect, was encapsulated in nanoparticles.
Experiments on cancer cell cultures have demonstrated that targeted delivery to the mitochondria increases the effectiveness of drugs by more than 100 times compared with systemic administration and by 5 times compared with complexes with nanoparticles that are tropic to the cell surface.
The natural compound curcumin has the ability to suppress the formation of plaques from the beta-amyloid protein, which is the main symptom of Alzheimer's disease. However, it degrades rapidly in the light and decomposes in the body in a very short time. The effect of curcumin encapsulated in polymer nanoparticles penetrating into mitochondria increased the survival of brain cells in culture in the presence of a compound stimulating the formation of amyloid plaques to almost 100%. When pure curcumin is introduced into the culture, this indicator is 67%, and when using a complex of curcumin and nanoparticles delivering it to the cell surface, it is 70%.
As part of another experiment, the researchers encapsulated inside the nanoparticles a drug for the treatment of obesity 2,4-DNP (2,4-dinitrophenol), which reduces the efficiency of the energy production process in mitochondria. The effect of this complex suppressed the synthesis of fats in the culture of preadipocytes by 67% compared with cells treated with a pure preparation, and by 61% compared with cells treated with a complex of the drug with nanoparticles tropic to the cell surface.
According to the authors, many diseases are associated with mitochondrial disorders, but very often drugs that affect the functioning of these organelles are not able to achieve their goal. At the same time, manipulations of the molecular structure of drugs can negatively affect their effectiveness, whereas targeted delivery into the mitochondria is the optimal way to increase it.
Currently, the developers are testing the new system on rodents and claim that the preliminary results are very encouraging.
The article by Sean Marrachea and Shanta Dhar Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Georgia:
UGA researchers boost efficacy of drugs by using nanoparticles to target ‘powerhouse of cells’.
24.09.2012