'Nanobubbles' Plus Chemotherapy Equals Single-Cell Cancer Targeting
Using light-harvesting nanoparticles to convert laser energy into "plasmonic nanobubbles," researchers at Rice University, the University of Texas MD Anderson Cancer Center, and Baylor College of Medicine (BCM) are developing new methods to inject drugs and genetic payloads directly into cancer 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.
This work was led by Rice's Dmitri Lapotko. He and his colleagues have published their work in two papers appearing in the journals Advanced Materials and PLoS One.
Rice's nanobubbles are not nanoparticles; rather, they are short-lived events. The nanobubbles are tiny 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.
This method, which has yet to be tested in animals, will require more research before it might be ready for human testing, said Lapotko, faculty fellow in biochemistry and cell biology and in physics and astronomy at Rice.
The plasmonic nanobubbles are generated when a pulse of laser light strikes a plasmon, a wave of electrons that sloshes back and forth across the surface of a metal nanoparticle. By matching the wavelength of the laser to that of the plasmon, and dialing in just the right amount of laser energy, Dr. Lapotko's team can ensure that nanobubbles form only around clusters of nanoparticles in cancer cells. Using the technique to get drugs through a cancer cell's protective outer wall, or cell membrane, can dramatically improve the drug's ability to kill the cancer cell.
To form the nanobubbles, the researchers must first get the gold nanoclusters inside the cancer cells. The scientists 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. 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 research is funded by the National Institutes of Health and is described in the following recent papers: "Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems," was published in PLoS ONE, and "Plasmonic nanobubbles enhance efficacy and selectivity of chemotherapy against drug-resistant cancer cells," was published in Advanced Materials.