Large Hopes, Small Tools

Tiny "Ninja" nanoparticles selectively target and then fight cancer cells from within.

Charles Daghlian, director of Dartmouth’s Electron Microscope Facility, uses Dartmouth's Tecnai Electron Microscope. Nanoparticles are visible only through an electron microscope.

Nanoparticles can slip though the lining of cancer cells and, once inside, release anti-cancer agents. Researchers are using these tiny tools to deliver heat inside cancer cells to kill them without damaging adjacent healthy cells.

The concept behind cancer nanotechnology has captured children's imaginations for years. A magical school bus travels through the body's vascular system. Horton, an elephant, discovers a microscopic world inside a speck of dust. These tales of tininess drive us to consider the smallest systems imaginable, beyond our comprehension. This is the realm of cancer nanotechnology, visible only through an electron microscope.

Cancer nanotechnology, where the head of a pin is a galaxy
nanoparticles tumors

How heating a cancer cell from the inside activates the body’s immune system to fight off tumor growth.

If you have one nanoparticle (a standard nanoparticle may be from 20 to 100 nanometers in size) you will need up to 300,000 more to fill one cancer cell. The nanoparticle is engineered to slip through the protective lining of the cancer blood vessel, and then it is selectively taken into a cancer cell through a specific cell membrane process. Once inside the cell it can deliver an anti-cancer agent.

As a National Cancer Institute designated Center of Cancer Nanotechnology Excellence, Norris Cotton Cancer Center (NCCC) is one of only a handful of cancer centers nationwide investigating how these small tools can be used to eliminate tumors. Our researchers are exploring how nanotechnology can be used in safe and effective ways, and they are combining this new technology with existing therapies like chemotherapy and radiation. A key goal is to create a nanoparticle that is lethal to a cancer cell but will not get into healthy cells or organs (like the liver) as it enters or leaves the body. Dartmouth engineers, scientists, and physicians will soon take nanotechnology out of laboratory and into clinical tests with volunteer patients.

Nanoparticles corrode cancer cells from the inside

In one recent NCCC study, scientists injected a nanoparticle containing iron oxide into a mouse tumor. Then they exposed the tumor to a magnetic field, which caused the iron oxide particle to give off heat inside the cell. The heat killed the cancer cell.

"This is an entirely new tact with different capability from anything we've done before," said P. Jack Hoopes, DVM, PhD, professor of Surgery, Radiation Oncology, at the Geisel School of Medicine at Dartmouth, Adjunct Professor and Senior Lecturer at the Thayer School of Engineering, and one of the principal investigators of Dartmouth's Center of Nanotechnology Excellence. "We are using targeted heat inside the cell."

Other laboratory research is taking this one step further by studying how heated nanoparticles might jump-start the body's immune system to fight cancer.

Nanoparticles improve body's offensive and defensive abilities

When researchers injected iron oxide nanoparticles into mice tumors and then exposed them to magnetic energy, it activated antigen-presenting dendritic cells in the body's immune system. Dendritic cells are like "quarterbacks" for the body's immune system, calling for quick coordinated protection against an attack.

The "quarterback" cells show the defensive "killer" T-cells how to attack tumor cells and to send out an alert to engage other cells in the fight. The combination of offense and defense reduced the risk of recurrence and discouraged spreading or metastasis of the cancer in the mice. This response occurred in the primary tumor treated as well as those in distant sites, and this restricted growth was observed for one month following overheating.

"The study demonstrates that controlled heating of one tumor can stimulate an immune response that attacks another tumor that has not had the heat treatment," said Steve Fiering, PhD, Norris Cotton Cancer Center researcher and professor of Microbiology and Immunology, and of Genetics at the Geisel School of Medicine. "This is one way to try to train the immune system to attack metastatic tumors that may not be recognized yet."

The experiment included mouse colon and melanoma cancers. Tumors responded to the heat by growing more slowly or disappearing completely. A high temperature was better at eliminating primary tumors, however the higher temperature did not activate the immune system as well. Treatment of larger primary tumors generated a stronger immune response.

"None of this work would have been possible without the support of The Prouty," said Hoopes. This annual signature fundraiser provided seed funding for nanotechnology, which helped it get off the ground and secure its place as a center of excellence. "All those fundraisers and volunteers who walk and bike for cancer research every July have made this promising science possible."

Dartmouth has been designated as a Center of Cancer Nanotechnology Excellence (CCNE) with a five-year, $12.8 million grant from the National Cancer Institute (NCI). The CCNE places Dartmouth among top centers in cancer nanotechnology research nationwide and takes full advantage of Dartmouth's culture of cross-disciplinary collaboration. CCNEs are tasked with integrating nanotechnology into basic and applied cancer research in order to provide new solutions for the diagnosis and treatment of cancer.

March 24, 2014