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George Kovacik

Phone: 281.841.7119

ggkovacik@houstonmethodist.org


Tiny Transports Successfully ‘Deliver’ to Diseased Hearts
If it’s true that good things come in small packages, then researchers from the U.S. and Mexico, led by physicians at Houston Methodist Hospital, may soon have some good news for patients suffering with chronic heart failure.

In a recent paper in the European Journal of Heart Failure, the team described how it capitalized on a process for manufacturing integrated circuits at the nanometer (billionth of a meter) level to engineer tiny particles known as nanovectors. The researchers demonstrated that their Lilliputian hemispheres could associate with diseased cardiac tissue cells in mice, enter them, and then be directed toward targeted areas within those cells—a first step toward using nanovectors for delivering drug or genetic therapies in the future.

A number of promising treatments incorporating small molecular-size chemical compounds or genetic materials have recently been developed for patients with chronic heart disease. However, the use of these agents has been hindered by their inability to reach the diseased myocardium in high enough concentrations to be effective or, in the case of gene therapies, get to the failing tissues at all. To solve the problem, the Houston Methodist-led team borrowed a proven technique from the fight against cancer.

“We know that nanovectors have been successfully used to deliver drug and genetic therapies into tumors because those cells are more permeable than normal ones,” said Guillermo Torre-Amione, M.D., Ph.D., senior author and director of the Heart Failure Research Laboratory at Houston Methodist DeBakey Heart & Vascular Center. “Diseased heart tissues, like tumors, are not as tightly connected as normal myocardium, so we believed that the same factors allowing nanovectors into cancer cells would apply here as well.”

Using photolithography (printing a pattern into a material using light, similar to photography) and electrochemical etching (cutting the pattern away from the material using chemicals)—both techniques commonly used to create circuits on semiconductor chips—the researchers fabricated silicon hemispheres 1,000 nanometers (1/100 the thickness of a sheet of paper) in size. They filled the bowl-shaped hollows of these nanovectors with even smallernanoparticles loaded with fluorescent dye to simulate a transported drug or genetic therapy. The vectors and their cargo were then injected into the cardiac tissues of mice with heart disease to test the effectiveness of the delivery system. 

“We found that the nanovectors successfully passed through the membranes of the diseased myocytes [muscle cells] and non-myocytes, accumulated inside and deposited their nanoparticles and dye on target,” said Torre-Amione. “The process was completely non-toxic; normal heart tissues were not entered and therefore, their cell functioning was unaffected.”

Next, the research team plans to refine its nanovector system and start testing its ability to deliver therapeutic chemicals or genetic materials to diseased heart tissues in humans. Torre-Amione said that he and his colleagues also may apply the technique to treat cardiac fibrosis (thickening of the heart valves) and cardiac muscle cells with weak contracting ability.

This work was supported by funding from the George and Angelina Kostas Research Center for Cardiovascular Nanomedicine, Department of Defense grants (W81XWH-09-1-0212 and W81XWH-12-1-0414), and National Institute of Health grants (U54CA143837 and U54CA151668).

The researchers who collaborated with Torre-Amione on the European Journal of Heart Failure paper were: Guillermo U. Ruiz-Esparza, Victor Segura-Ibarra, Kenji Yokoi, Dickson K. Kirui, Francisca E. Cara, Mauro Ferrari and Elvin Blanco (Houston Methodist Research Institute, Houston, Texas); Jesus Paez-Mayorga, Carlos E. Guerrero-Beltrán and Gerardo Garcia-Rivas (Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey, Mexico); Andrea M. Cordero-Reyes, Keith A. Youker, Ana S. Cruz-Solbes and Javier Amione-Guerra (DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas); and Rita E. Serda and Jose H. Flores-Arredondo (Baylor College of Medicine, Houston, Texas).

To speak with Guillermo Torre-Amione, M.D., Ph.D., contact George Kovacik, Houston Methodist, at 281.841.7119 or ggkovacik@houstonmethodist.org. For more information about Houston Methodist, visit houstonmethodist.org. Follow us on Twitter and Facebook.

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“A specifically designed nanoconstruct associates, internalizes, traffics in cardiovascular cells, and accumulates in failing myocardium: a new strategy for heart failure diagnostics and therapeutics” European Journal of Heart Failure Volume 18, Issue 2, February 2016, Pages: 169–178, Guillermo U. Ruiz-Esparza, Victor Segura-Ibarra, Andrea M. Cordero-Reyes, Keith A. Youker, Rita E. Serda, Ana S. Cruz-Solbes, Javier Amione-Guerra, Kenji Yokoi, Dickson K. Kirui, Francisca E. Cara, Jesus Paez-Mayorga, Jose H. Flores-Arredondo, Carlos E. Guerrero-Beltrán, Gerardo Garcia-Rivas, Mauro Ferrari, Elvin Blanco and Guillermo Torre-Amione. Article first published online: 7 JAN 2016, DOI: 10.1002/ejhf.463.