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Cancer therapy -- Nanokey opens tumors to attack
Date:11/14/2012

metastases."

A new strategy employing gene therapy could provide a solution to this problem. The idea is to deliver the gene for TNFα directly and specifically to the tumor cells. If this worked, the tumor cells themselves could produce and secrete the cytokine, ensuring that its local concentration becomes sufficiently high to permeabilize the blood vessels only in the immediate vicinity of the tumor. "We first designed a version of the TNFα gene that allows for the production of large amounts of the protein," Dr. Baowei Su, first author on the study, explains.

Shielding the drug from the organism

In collaboration with researchers at the Technische Universitt Mnchen and the Helmholtz Center Munich, the LMU team constructed a form of the gene which, in contrast to the normal version, is unlikely to induce non-specific inflammation. The plasmid was then incorporated into special nanoparticles, which not only protect the DNA from inactivation during its journey through the bloodstream, but also allow it to be targeted to the tumor. Experiments carried out on cell cultures confirmed that tumor cells treated with these particles synthesize large amounts of TNFα.

Treatment with the loaded nanoparticles alone, however, had only a moderate effect on tumor cells, but when they were administered in combination with the DNA-intercalating drug doxorubicin, the impact on tumor cell growth was markedly enhanced. Under the trade name Doxil, doxorubicin, which inhibits DNA replication, is available in a liposome-encapsulated form. Incorporating the drug into liposomes of 100 nm in diameter reduces side-effects and increases its half-life in the circulation, making it more effective than unencapsulated formulations.

No evidence for drug resistance

When mice with neuroblastoma, or mice that had received a xenograft of a human liver tumor, were first exposed to nanoparticles carrying the TNFα gene and su
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Contact: Kathrin Bilgeri
kathrin.bilgeri@lmu.de
49-892-189-6938
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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