Gold-Based HDL-Nanoparticles Kill Lymphoma Cells without Drugs

Synthetic nanoparticles that mimic the look and behavior of HDLs (high-density lipoproteins) have been found to act as potent killers of human B-cell lymphoma cells both in cultures and in a mouse model without the necessity of associated anticancer drugs.

Investigators at Northwestern University (Chicago, IL, USA) synthesized HDL biomimetic nanoparticles capable of binding cholesterol. These structures used a gold nanoparticle core as template for the assembly of a mixed phospholipid layer that adsorbed and intercalated molecules of apolipoprotein A-I. These synthesized structures had the general size and surface composition of natural HDL and, importantly, were able to bind free cholesterol.

Some cancer cells express receptors for HDLs due to their increased need for cholesterol. Accordingly, HDL-nanoparticles could be used as vehicles to deliver therapeutic agents to cancer cells expressing these HDL receptors. Moreover, a surprising study published in the January 23, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) revealed that the HDL-nanoparticles by themselves were toxic to B-cell lymphoma cells without the necessity of associated anticancer drugs.

Like natural HDLs, the biomimetic HDL-nanoparticles targeted scavenger receptor type B-1, a high-affinity HDL receptor expressed by lymphoma cells. Use of the gold nanoparticle template enabled differential manipulation of cellular cholesterol flux, promoting transport of cholesterol away from the cells while limiting cholesterol delivery to the cells. This combination of scavenger receptor type B-1 binding and relative cholesterol starvation selectively induced apoptosis and ultimately death of the cancer cells.

In mice bearing B-cell lymphoma xenografts, treatment with HDL-nanoparticles selectively inhibited tumor growth.

"This has the potential to eventually become a nontoxic treatment for B-cell lymphoma, which does not involve chemotherapy," said contributing author Dr. Leo I. Gordon, professor of hematology and oncology at Northwestern University. "It is an exciting preliminary finding."

The investigators reported being particularly encouraged by early data showing that the HDL nanoparticles did not appear to be toxic to other human cells normally targeted by HDLs, normal human lymphocytes, or to mice.

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