To fight cancer, nanoparticles need a better disguise

May 22, 2013 | by Nicole White

In  the search for better ways to deliver powerful chemotherapy drugs only to tumors, leaving healthy tissue unscathed, nanoparticles are emerging as a promising tool. These tiny particles can be loaded with powerful chemotherapy drugs that, ideally, can be delivered directly to the cancer site.  But the delivery only can be completed if the packages avoid detection by healthy cells.

 

To deliver nanoparticles carrying chemotherapy drugs directly to the tumor, City of Hope researchers are suggesting a better disguise. Shown in this illustration from the cover of the Journal of Materials Chemistry B, gold nanoparticles are cloaked in a protective coating that allows them to bypass healthy cells. But, when the particles encounter tumor cells, a tumor enzyme is drawn to the peptide in the coating. The enzyme chops through the cloak, allowing the drug-carrying particles to be ingested by the cell. To deliver nanoparticles carrying chemotherapy drugs directly to the tumor, City of Hope researchers are suggesting a better disguise. Shown in this illustration from the cover of the Journal of Materials Chemistry B, gold nanoparticles are cloaked in a protective coating that allows them to bypass healthy cells. But, when the particles encounter tumor cells, a tumor enzyme is drawn to the peptide in the coating. The enzyme chops through the cloak, allowing the drug-carrying particles to be ingested by the cell.

 

City of Hope scientists may have found a way to ensure their packages arrive safely. They recently published a paper in the Journal of Materials Chemistry B outlining a new strategy for disguising these drug-carrying nanoparticles so that they will drop their therapeutic drugs directly at the tumors – escaping notice from cells that want to filter them to the liver.

In their study, researchers applied a coating to gold nanoparticles to shield them from being gobbled up – a tactic that’s been used before but that still results in most of the particles collecting in the liver instead of at the tumor sites. However, this time researchers used a more cunning disguise: They masked the particles in a coating marked with a specific molecule that triggered the tumor itself to attack the nanoparticles, break through their shield and ingest them.

 

“If you can control when the particle is disguised and when it is revealed, then you can control where it’s going to release its drugs,” said Jacob Berlin, PhD, assistant professor in the Department of Molecular Medicine at City of Hope, and lead author of the paper. “There’s more work to be done, but this is a good proof-of-concept.”

In the study, researchers focused on a tumor enzyme that breaks down healthy tissue to make way for tumor cells. To do so, it chops up one particular peptide. When the enzyme encountered one of the disguised particles, it recognized the peptide and chopped through the coating, allowing the cancer cell to recognize, attack and consume the particle.

In the cell study, the delivery of the particles into cancer cells increased by more than 100 times when the tumor-specific enzyme was present.

Berlin said, going forward, he would like to explore what drugs can be delivered using this approach and whether the concept can be adapted. Other molecules, proteins and enzymes common to tumors could potentially be used as triggers to remove the coating from drug-carrying particles, he said.

The study was co-authored by Anil Suresh, Ph.D.; Yiming Weng, Ph.D., postdoctoral fellow; Zhuo Li, Ph.D., assistant research professor; Ricardo Zerda, senior research associate; Desiree Van Haute, graduate student; and John C. Williams, Ph.D., associate professor.

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