Using light-harvesting nanoparticles to convert laser energy into “plasmonic nanobubbles,” Dmitri Lapotko of Rice University, Malcolm K. Brenner of Baylor College of Medicine, and their colleagues are creating methods to inject drugs and genetic payloads directly into cancer cells without affecting nearby healthy cells. In tests on drug-resistant cancer cells, the researchers found that delivering chemotherapy drugs with nanobubbles was up to 30 times more deadly to cancer cells than traditional drug treatment and required less than one-tenth the clinical dose. The researchers recently reported their findings in the July issue of Biomaterials (DOI:10.1016/j.biomaterials.2012.03.077; p. 5441).

Delivering drugs and therapies selectively so they affect cancer cells but not healthy cells nearby is a major challenge in drug delivery. Sorting cancer cells from healthy cells has been successful, but it is both time-consuming and expensive. Researchers have also used nanoparticles to target cancer cells, but nanoparticles can be taken up by healthy cells, so attaching drugs to the nanoparticles can also kill healthy cells.

Nanobubbles are not nanoparticles; rather, they are short-lived events. The nanobubbles are pockets of air and water vapor that are created when laser light strikes a cluster of nanoparticles and is converted instantly into heat. The bubbles form just below the surface of cancer cells. As the bubbles expand and burst, they briefly open small holes in the surface of the cells and allow cancer drugs to rush inside. The same technique can be used to deliver gene therapies and other therapeutic payloads directly into cells. “We are delivering cancer drugs or other genetic cargo at the single-cell level,” said Lapotko.

To form the nanobubbles, the researchers must first place the gold nanoclusters inside the cancer cells. The researchers do this by tagging individual gold nanoparticles with an antibody that binds to the surface of the cancer cell. Cells ingest the gold nanoparticles and sequester them together in tiny pockets just below their surfaces. The gold nanoparticles are then irradiated with single short laser pulses of 70 ps, at 532 nm. The optical energy is converted to thermal energy through plasmon resonance, resulting in heat being released by the nanoparticles, evaporating their liquid environment, and producing nanobubbles.

While a few gold nanoparticles are taken up by healthy cells, the cancer cells take up far more, and the selectivity of the procedure owes to the fact that the minimum threshold of laser energy needed to form a nanobubble in a cancer cell is too low to form a nanobubble in a healthy cell.

“The nanobubble injection mechanism is an entirely new approach for drug and gene delivery,” Brenner said. “It holds great promise for selectively targeting cancer cells that are mixed with healthy cells in the same culture.”