'Good cholesterol' nano-particles seek and destroy cancer cells

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

Synthetic HDL nanoparticles of with small interfering cancer promoting genes of of RNA specifically to silence to bring loaded shrunk or ovarian tumors in mice destroyed, a research team led by scientists from the University of Texas MD Anderson Cancer Center and the University of North Texas Health Science Center reports in the April issue of neoplasia.

"RNA interference has great therapeutic potential, but deploying it for cancer cells has been problematic,", author of the study and MD said Anil Sood, m.d., senior Anderson's Director of ovarian cancer research and Co-Director of the Center for RNA interference and non-coding RNA at MD Anderson. "That combine SiRNA with HDL is an efficient way, these molecules to obtain their goals." "This study has several important implications in the ability to fight certain types of cancer."

Together on Lacko's original insight on the HDL developed potential for cancer drug delivery Sood and András Lacko, PhD., Professor of molecular biology and Immunology at the UNT Health Science Center, the nano-particles.

The next step is to prepare you for human clinical trials, said the two scientists. "If we out 70, 80 or 90% of tumors without drugs, normal tissue accumulation mice knock can, it is likely that many cancer patients in the long term have benefited from this new type of treatment," said Lacko.

Only cancer and liver cells express HDL receptor

Previous studies have shown that cancer cells attract and HDL maid through the high degree of its receptor, SR-B1. As cancer cells in HDL, they grow and multiply. The only other site in the body, making SR-B1 receptor is the liver. This selectivity for cancer cells protects normal, healthy cells of side effects.

Earlier attempts, SiRNA from Lipsomes and other nano-particles has been provide by toxicity and other concerns disabled. The tiny bits of RNA, which directed way can genes highly rules, not just, for example be injected.

"SiRNA is not in a nano-particles, it gets broken down and eliminated, before you can take effect", Sood said. "HDL is fully biocompatible and improve the security over other nano-particles."

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

Fewer and smaller tumors, less toxicity

With rHDL as a delivery method has other advantages. rHDL was not shown, cause that immunological reactions, help reduce possible side effects, minimize Lacko said, and it is longer in circulation as other drug formulations or lipoproteins. Also, because SR-B1 only in the liver is found, help a rHDL vehicle handle this body block and metastasis.

Researchers confirmed the distribution of SR-B1 first, and the inclusion of rHDL nanoparticles in mice injected with cancer cells. They found that SiRNA was evenly distributed in about 80 percent of the treated tumour. As expected, the nano-particles in the liver with minimal or no delivery to the brain, heart, lungs, kidney or spleen accumulated. Security studies showed that the inclusion in the liver caused no side effects.

SiRNA tailored to the individual conditions use, shut down the researchers separately the STAT3 gene and FAK in different types of treatment-resistant ovarian cancer tumors. STAT3 and FAK are important to cancer growth, progression and metastasis; However, they play important roles in normal tissue of as targeting accuracy is crucial.

Alone the SiRNA/rHDL formulation reduces the size and number of tumors of 60 to 80 percent. Combinations with chemotherapy caused cuts over 90 percent.

Traditional approaches to the goal of STAT3 limited success met have, Sood said. FAK, the over expressed in Colorectal, breast, ovarian, thyroid and prostate cancer, is particularly aggressive in ovarian cancer and one of the reasons for its poor survival rate. While previous attempts have targeted FAK with liposomal nanoparticles or small molecule inhibitors, provided these methods are not tumor specific and are rather normal cells, damaging the scientists.

Next step: clinical studies

"In order to help to accelerate progress in the study to a clinical setting, we have identified 12 genes as biomarkers for the response to STAT3 targeted therapy," Sood said. "Next with the National Cancer Institute of Nano particle characterization lab one formulation of the HDL/SiRNA nanoparticle develop for human medicinal products we work."

MD Anderson and UNT have applied for a patent for the method of nano-particles. These agreements are managed by M.D. Anderson and the University of North Texas HSC according to institutional conflict of interest guidelines.

Source: University of Texas M. D. Anderson Cancer Center