‘Nanobubbles’ deliver chemotherapy drugs directly to cancer cells

April 10, 2012

Tumor treated by plasmonic nanobubbles (credit: Rice University)

In tests on drug-resistant cancer cells, researchers have found that delivering chemotherapy drugs and and genetic payloads with “plasmonic nanobubbles” injected directly into cancer cells was up to 30 times more deadly to cancer cells than traditional drug treatment and required less than one-tenth the clinical dose.

“We are delivering cancer drugs or other genetic cargo at the single-cell level,” said Rice’s Dmitri Lapotko, a biologist and physicist whose plasmonic nanobubble technique is the subject of four new peer-reviewed studies.

“By avoiding healthy cells and delivering the drugs directly inside cancer cells, we can simultaneously increase drug efficacy while lowering the dosage,” he said.

How nanobubbles deliver drugs to cancer cells

The researchers at Rice University, the University of Texas MD Anderson Cancer Center, and Baylor College of Medicine (BCM) are using “plasmonic nanobubbles.” These are tiny pockets of air and water vapor that are created when laser light strikes a plasmon (a wave of electrons that sloshes back and forth across the surface of a gold nanoparticle, in this case) and is converted instantly into heat.

After injecting drugs, plasmonic nanobubbles are generated from laser light (blue) and burst inside cancer cells, opening up holes for drugs to rush inside (credit: Rice University)

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.

To get the gold nanoclusters inside the cancer cells, the scientists tag 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 same technique can be used to deliver gene therapies and other therapeutic payloads directly into cells, using selective genetic modification of human T-cells, for example.

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.

Ref.: Ekaterina Y. Lukianova-Hleb et al. Plasmonic nanobubble-enhanced endosomal escape processes for selective and guided intracellular delivery of chemotherapy to drug-resistant cancer cells. Biomaterials, 2012; 33 (6): 1821 DOI:10.1016/j.biomaterials.2011.11.015.

Ref.: Ekaterina Y. Lukianova-Hleb et al. Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems. PLoS ONE, 2012; 7 (4): e34537 DOI:10.1371/journal.pone.0034537.

Ref.: Ekaterina Y. Lukianova-Hleb et al. Plasmonic Nanobubbles Enhance Efficacy and Selectivity of Chemotherapy Against Drug-Resistant Cancer Cells. Advanced Materials, 2012; DOI: 10.1002/adma.201103550.