Research could lead to new type of treatment for pancreatic cancer based on gold nanoparticles

A diagnosis of pancreatic cancer is often a death sentence because chemotherapy and radiation have little impact on the disease. In the U.S. this year, some 53,000 new cases will be diagnosed, and 42,000 patients will die of the disease, according to the National Institutes of Health. But research now being reported in ACS Nano could eventually lead to a new type of treatment based on gold nanoparticles.

Scientists have previously studied these tiny gold particles as a vehicle to carry chemotherapy drug molecules intotumors or as a target to enhance the impact of radiation on tumors. In addition, Priyabrata Mukherjee and colleagues previously found that gold nanoparticles themselves could limit tumor growth and metastasis in a model of ovarian cancer in mice.

Now, the team has determined that the same holds true for mouse models of pancreatic cancer. But interestingly, the new work revealed details about cellular communication in the area surrounding pancreatic tumors. By interrupting this communication -- which is partly responsible for this cancer's lethal nature -- the particles reduced the cell proliferation and migration that ordinarily occurs near these tumors. Gold nanoparticles of the size used in the new study are not toxic to normal cells, the researchers note.

Nanotechnology researchers prove two-step method for potential pancreatic cancer treatment

The dual-wave nanotherapy method employed by Drs. Nel and Meng in their research uses two different kinds of microscopic particles (nanoparticles) intravenously injected in a rapid sequence into the vein of the tumor-bearing mouse. The first wave of nanoparticles carries a substance that removes the pericytes' vascular gates to access the pancreatic cancer cells and the second wave carries the chemotherapy drug that kills the cancer cells.

Drs. Nel and Meng and their colleagues Dr. Jeffrey Zink, UCLA professor of chemistry and biochemistry and Dr. Jeffrey Brinker, University of New Mexico professor of chemical and nuclear engineering, sought to contain chemotherapy in nanoparticles that could more directly target pancreatic cancer cells, but they needed to find a way for those nanoparticles to get through the sites of vascular obstruction caused by the pericytes, which restricts access to the cancer cells. Through experimentation they discovered they could interfere with a cellular signaling pathway (the communication mechanism between cells) that governs the pericyte attraction to the tumor blood vessels. By making nanoparticles that effectively bind a high load of the signaling pathway inhibitor, they developed a first wave of nanoparticles that separates the pericytes from the endothelial cells (on the blood vessel). This opens the vascular gate for the next wave of nanoparticles, which carry the chemotherapeutic agent to the cancer cells inside the tumor.

To test this two-wave nanotherapy, the researchers used immuno-compromised mice that were used to grow human pancreatic tumors (called xenografts) under the mouse skin. With the two-wave method, the xenograft tumors had a significantly higher rate of shrinkage compared to those exposed to chemotherapy given the standard way as a free drug or carried in nanoparticles without first wave treatment.

"This two-wave nanotherapy is an existing example of how we seek to improve the delivery of chemotherapy drugs to their intended targets using nanotechnology to provide an engineered approach," said Nel, chief of the division of nanomedicine. "It shows how the physical and chemical principles of nanotechnology can be integrated with the biological sciences to help cancer patients by increasing the effectiveness of chemotherapy while also reducing side effects and toxicity. This two-wave treatment approach can also address biological impediments in nanotherapies for other types of cancer."

Ref : http://pubs.acs.org/doi/abs/10.1021/nn404083m

Nanotechnology researchers prove two-step method for potential pancreatic cancer treatment