'Good Cholesterol' Nanoparticles Seek And Destroy Cancer Cells

High-density lipoprotein's hauls excess cholesterol to the liver for disposal, but new research suggests "good cholesterol" can also act as a special delivery vehicle of destruction for cancer.

Synthetic HDL nanoparticles loaded with small interfering RNA to silence cancer-promoting genes selectively shrunk or destroyed ovarian cancer tumors in mice, a research team led by scientists from The University of Michigan MD Anderson Cancer Middle and the University of North Michigan Health Science Middle reports in the April edition of Neoplasia.

"RNA interference has great therapeutic potential but delivering it to cancer cells has been problematic," said Anil Sood, M.D., the study's senior author and MD Anderson's director of Ovarian Cancer Research and co-director of the Middle for RNA Interference and Non-Coding RNA at MD Anderson. "Combining siRNA with HDL provides an efficient way to get these molecules to their targets. This study has several important implications in the ability to fight definite cancers."

Sood and Andras Lacko, Ph.D., professor of Molecular Biology and Immunology at UNT Health Science Middle, jointly developed the nanoparticles, which build on Lacko's original insight about HDL's potential for cancer drug delivery.

The next step is to prepare for human clinical trials, the six scientists said. "If they can knock out 70, 80 or 90 percent of tumors without drug accumulation in normal tissues in mice, it is likely that plenty of cancer patients may benefit from this new type of treatment in the long run," Lacko said.

Only cancer and liver cells express HDL receptor

Earlier attempts to deliver siRNA by lipsomes and other nanoparticles have been hampered by toxicity and other concerns. The small bits of RNA, which regulate genes in a highly targeted fashion, cannot basically be injected, for example.

Earlier studies have shown that cancer cells attract and scavenge HDL by producing high levels of its receptor, SR-B1. As cancer cells take in HDL, they grow and proliferate. The only other site in the body that makes SR-B1 receptor is the liver. This selectivity for cancer cells protects normal, healthy cells from side effects.

"If siRNA is not in a nanoparticle, it gets broken down and excreted before it can be effective," Sood said. "HDL is biocompatible and is a safety improvement over other types of nanoparticles."

The team developed a synthetic version of HDL, called rHDL, because it is more stable than the natural version.

Using rHDL as a delivery system has other advantages as well. rHDL has not shown to cause immunologic responses, helping to minimize potential side effects, Lacko said, and it exhibits longer time in circulation than other drug formulations or lipoproteins. Also, because SR-B1 is found only in the liver, an rHDL vehicle will help block and treat metastasis to that organ.