Researchers at the University of Georgia have developed nanoparticles that are able to deliver drugs targeting a specific cellular organelle. The mitochondria, the "powerhouse of cells," is the organelle where the process of cellular respiration mainly occurs, generating the energy needed to fuel the cell. Through cell cultures injected with nanoparticles, researchers have found that the use of these particles targeting the mitochondria improved the efficacy of cancer, Alzheimer's disease, and obesity medication.
"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 author and assistant professor of chemistry at UGA, Shanta Dhar.
Dhar and co-author Sean Marrache formed nanoparticles from a biodegradable, FDA-approved polymer, which encapsulated drugs such as the cancer medication lonidamine. Lonidamine reduces cellular respiration in the mitochondria and inhibits a form of vitamin E. By utilizing the mitochondrial-targeting nanoparticles, the results of the study showed that the efficacy of the drug increased over 100 times more than the medication alone and five times more than other nanoparticles targeting extracellular components.
The delivery of another drug, curcumin, used for Alzheimer's, has been greatly improved by the new breakthrough. Previously, curcumin would inhibit amyloid plaque formation in the brain, but would also denature in light and degrade quickly in the body. Now, with encapsulated curcumin in nanoparticles, neurons in culture would be able to survive while in contact with a plaque-inducing compound. Almost all cells with these curcumin mitochondria-targeting nanoparticles survived, whereas only 67 percent did with only curcumin, and 70 percent did with the non-mitochondria-targeting nanoparticles.
Obesity drug 2,4-DNP also was enhanced through this process. 2,4-DNP lowers energy production in the mitochondria, and by targeting this specific organelle with the nanoparticles, fat production of preadipocyte cells was reduced by 67 percent when compared to 2,4-DNP alone. It decreased by 61 percent compared to nanoparticles targeting extracellular components.
Marrache states, "A lot of diseases are associated with dysfunctional mitochondria, but many of the drugs that act on the mitochondria can't get there. 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."
The nanoparticles function by averting the process of degradation within the cell. When particles enter a cell, they must pass through the endosome, an organelle responsible for sorting and redirecting particles to other organelles, such as the lysosome. Dhar and Marrache worked to develop nanoparticles that would pass through the endosomes and avoid the lysosome, where foreign particles and wastes are disposed and digested.
As of now, the researchers will continue to test the delivery system in rodents, advancing both nanotechnology and pharmaceutics to a new level.
Image by Libertas Academica, courtesy of Creative Commons licensing.
