Folic Acid Guides Anti-Cancer Nanoparticles

Cancer researchers have created a "magic bullet” drug by attaching the powerful anti-cancer agent methotrexate to a nanoparticle coated with molecules of folic acid, which specifically target the drug towards cancer cells' folic acid receptors.

Investigators at the University of Michigan (Ann Arbor, USA) used a PAMAM dendrimer nanoparticle as the backbone of the drug. PAMAM dendrimers represent a new class of macromolecular architecture called "dense star” polymers. Unlike classical polymers, dendrimers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and shape characteristics, and a highly functionalized terminal surface. The powerful anti-cancer agent methotrexate was added to kill the tumor cells, while molecules of folic acid ensured that the drug molecules would be bound and absorbed specifically by the target tumor. Fluorescent imaging agents were also attached to enable the researchers to track the spread of the drug.

Drug conjugates were injected into immunodeficient mice bearing human KB tumors that overexpress folic acid receptor. Results reported in the June 15, 2005, issue of Cancer Research revealed that after four days of drug administration the folic acid-conjugated nanoparticles became concentrated in the tumor and liver tissue. Particles without folic acid were not concentrated, and prior injection of free folic acid prevented concentration of the folic acid-labeled nanoparticles.

All free nanoparticles were quickly filtered from the blood by the kidneys and eliminated in the urine. No evidence was found to indicate that nanoparticles were able to leave the bloodstream and enter the brain. The nanoparticles did not appear to generate an immune response in mice in the study.

In a trial lasting 99 days, 30% to 40% of the mice given the methotrexate nanoparticles survived, while all the mice receiving free methotrexate died – either from overgrowth of the tumor or from toxic effects of the drug.

"This is the first study to demonstrate a nanoparticle-targeted drug actually leaving the bloodstream, being concentrated in cancer cells, and having a biological effect on the animal's tumor,” said senior author Dr. James R. Baker Jr., professor of biologic nanotechnology at the University of Michigan. "Targeting drugs directly to cancer cells reduces the amount that gets to normal cells, increases the drug's anti-cancer effect, and reduces its toxicity. By improving the therapeutic index of cancer drugs, we hope to turn cancer into a chronic, manageable disease.”



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