DNA Nanoparticles Effectively Kill Pancreatic Cancer Cells in Culture

Pancreatic cancer is one of the most deadly types of cancer, and to date no effective chemotherapy is available.

The approach described in the October 2008 online edition of the journal Cancer Biology & Therapy is based on the membrane protein mesothelin, a 40-kDa protein present on normal mesothelial cells and overexpressed in several human tumors. The mesothelin gene encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycosylphosphatidyl inositol linkage, and a 31-kDa-shed fragment named megakaryocyte-potentiating factor (MPF). Although it has been proposed that mesothelin is related to cell adhesion, the biological function of mesothelin is not known.

Investigators at Thomas Jefferson University (Philadelphia, PA, USA) modified a recently developed technique that in laboratory trials had successfully reduced the size of ovarian tumors following treatment with diphtheria toxin nanoparticles. They built nanoparticles comprising mesothelin DNA bound to the diphtheria toxin gene. Then, after confirming that a majority of pancreatic cancer cell lines and specimens taken from pancreatic tumors overexpressed mesothelin at the mRNA and protein levels, they treated cultures of pancreatic cancer cells with the nanoparticles.

The nanoparticles caused the protein manufacturing systems in more than 95% of treated cells to seize up, which resulted in death of the cells within five or six days of treatment. Normal cells, not overexpressing mesothelin were not harmed by the nanoparticles.

"For the pancreatic cancer world, this is very exciting,” said senior author, Dr. Jonathan Brody, assistant professor of molecular biology at Thomas Jefferson University. "There are no effective targeted treatments for pancreatic cancer, aside from surgery for which only a minority of patients qualify. We are in great need of translating the plethora of molecular information we know about this disease to novel therapeutic ideas.”

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