MAE researchers are hitting cancer where it hurts
Used in the past to destroy drug-resistant tumors, DNA origami – the nanoscale folding of DNA to create two- and three-dimensional shapes – is being used for the first time to deliver life-saving medicine to leukemia cells.
Associate Professor Carlos Castro is working with a team of researchers at The Ohio State University Wexner Medical Center to combat acute myeloid leukemia (AML) cells that have developed a resistance to the drug daunorubicin. Once the drug’s molecules are detected, the AML cells immediately pump them back out the opening of the cell wall.
By packaging the drugs in a capsule made of folded DNA, Castro and his team evade the AML cells’ defenses. Then, they can hit cancer where it hurts.
“DNA origami nanostructures have a lot of potential for drug delivery, [including] enabling new ways to study drug delivery,” said Castro. “For instance, we can vary the shape or mechanical stiffness of a structure very precisely and see how that affects entry into cells.”
His study, which was published in the journal Small, is co-authored by Professor John Byrd, the D. Warren Brown Chair of Leukemia Research. Other co-authors include Emily McWilliams, Matthew Webber, Randy Patton, Comert Kural and David Lucas.
His work with nanostructures doesn’t end there.
Castro is working alongside Assistant Professor Jonathan Song to prevent plasma leaks across individual blood vessels. By affixing nanostructures to cells, the duo’s nanotransducers can be designed to identify and measure the mechanical forces that orchestrate the assembly and patterning of tissue structures. This approach could also be used to embed sensors onto cell surfaces in order to measure physical or chemical cues of the local environment, which could be early indicators of cancer or other diseases.
Funded by an American Heart Association Innovative Research Grant, Castro and Song’s work with MAE graduate student Ehsan Akbari and alumna Molly Mollica (’16 MS) is forthcoming in the Advanced Materials journal.
Song is furthering the department’s cancer-fighting research by exploring blood vessels’ role in the growth of cancerous tumors. With support from a Pelotonia Idea Grant, Song will use microtechnology and tissue engineering to develop a disease model of advanced cancers. This, in turn, will enable him to use 3-D imaging to study the tumor conditions that create hostile cancer microenvironments.
The funding from Pelotonia, an annual cycling movement that has raised more than $130 million for cancer research, will empower Song and his team to develop therapeutic strategies for stopping tumor growth.
“Cancer is not only immensely difficult to treat, it is very challenging to study,” said Song, “We blend engineering design and cancer biology to ‘reverse engineer’ tumors in their microenvironment.”
Song’s collaborators include Mike Ostrowski, co-director of the Molecular Biology and Cancer Genetics program at The Ohio State University Comprehensive Cancer Center, and graduate student Alex Avendano.
An American Heart Association Scientist Development Grant will further advance his research’s impact. As the department’s first recipient of this prestigious award, Song will investigate the slow-moving flows within tissues and tumors that guide the formation of new blood and lymphatic vessels. Using this approach, he can help determine how molecular mechanics influence the patterning of blood and lymphatic vessel networks, which can have important applications for accelerating wound healing.
“We leverage the capacity of our microfabricated systems to precisely control the mechanical forces associated with fluid flow to enable new insights into the underlying biology,” said Song, who serves as the principal investigator of the Microsystems for Mechanobiology and Medicine Laboratory.
This work is also influencing the next generation of cancer-fighting engineers. Take Akbari, for example, who is advised by Song and has recently developed a sophisticated system that mimics the branching structure of blood vessels. Akbari’s insight into this unexplored area will allow him to truly predict where angiogenesis occurs based on the local fluid mechanical determinants.
By identifying the key players that drive tumor and cancer progression, MAE’s team of researchers will kill cancer’s fighting chance.