ONCOLOGY/NANOTECHNOLOGY: Solid or hollow? Particle characteristics determine whether cells are treated or killed

Researchers at Rice University have developed tunable plasmonic bubbles able to selectively destroy individual cells or inject them with substances such as drugs. The work hopes to someday replace multiple difficult processes now used to treat cancer, for example, with a single fast and simple procedure.

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Researchers at Rice University (Houston, TX) have developed tunable plasmonic bubbles able to selectively destroy individual cells (leaving neighbors unaffected) or inject them with substances such as drugs. The work hopes to someday replace multiple difficult processes now used to treat cancer, for example, with a single fast and simple procedure.

A short laser pulse applied to gold nanoparticles causes a plasmonic bubble to form around each one-a bubble that can kill a cancer cell by exploding it.1 Biochemist Dmitri Lapotko and colleagues found that this process offers much greater precision and selectivity compared with use of gold nanoparticles alone. They also found that a single laser pulse creates two sizes of bubble depending on the particle's form factor: large bubbles form around hollow gold nanoshells, while smaller bubbles form around solid gold nanospheres. Each of the large bubbles can selectively destroy a cell, while each of the small bubbles can punch a tiny, temporary pore in the wall of a cell and rapidly inject it with drugs or genes.

To demonstrate, the researchers placed 60-nm-wide hollow nanoshells in model cancer cells and stained them red. In a separate batch, they put 60-nm-wide solid nanospheres into the same type of cells and stained them blue. After suspending the cells together in a green fluorescent dye, they fired a single, wide laser pulse at the combined sample, and washed away the green stain. Viewing under a microscope showed that the red cells with the hollow shells had been blasted apart. The blue cells were intact, but green-stained liquid from outside had been pulled inside (see figure).

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(a) Rice University researchers placed hollow nanoshells in model cancer cells and stained them red, and solid nanospheres into the same type of cells and stained those blue. (b) After suspending the cells together in green fluorescent dye and firing a single, wide laser pulse at the sample, they saw that the red cells had been destroyed while the blue cells were intact—but green-stained liquid from outside had been pulled inside. (Images courtesy of the Plasmonic Nanobubble Lab/Rice University)

Lapotko says that a flow-through system (like one now being developed at Rice) can selectively process as many as 10 billion cells per minute, and the approach could advance cell and gene therapy and bone marrow transplantation. Most of these therapies require ex-vivo processing, and current methods are slow, expensive, and prone to high loss and poor selectivity. In fact, the long-term objective of a collaborative effort among Rice, Baylor College of Medicine (BCM), Texas Children's Hospital, and the University of Texas MD Anderson Cancer Center is to improve the outcome for patients needing this type of processing. "We'd like for this to be a universal platform for cell and gene therapy and for stem cell transplantation," he says.

According to Malcolm Brenner, professor of medicine and of pediatrics at BCM, director of BCM's Center for Cell and Gene Therapy, and research collaborator, says the approach could make quick work of complex processes. For instance, he said, "if I want to put something into a stem cell to make it turn into another type of cell, and at the same time kill surrounding cells that have the potential to do harm when they go back into a patient—or into another patient—these very tunable plasmonic nanobubbles have the potential to do that."

1. E. Y. Lukianova-Hleb, M. B. G. Mutonga, and D. O. Lapotko, ACS Nano., 6, 12, 10973–10981, doi:10.1021/nn3045243 (2012).

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