|
High-density lipoprotein's hauls excess cholesterol to the liver for disposal, but new research suggests "goodcholesterol" can also act as a special delivery vehicle ofdestruction for cancer . Synthetic HDL nanoparticles loaded with small interfering RNA tosilence cancer-promoting genes selectively shrunk or destroyed ovarian cancer tumors in mice, a research team led by scientists from TheUniversity of Texas MD Anderson Cancer Center and the University ofNorth Texas Health Science Center reports in the April edition ofNeoplasia. "RNA interference has great therapeutic potential but delivering itto cancer cells has been problematic," said Anil Sood, M.D., thestudy's senior author and MD Anderson's director of Ovarian CancerResearch and co-director of the Center for RNA Interference andNon-Coding RNA at MD Anderson. "Combining siRNA with HDL providesan efficient way to get these molecules to their targets. Thisstudy has several important implications in the ability to fightcertain cancers." Sood and Andras Lacko, Ph.D., professor of Molecular Biology andImmunology at UNT Health Science Center, jointly developed thenanoparticles, which build on Lacko's original insight about HDL'spotential for cancer drug delivery. The next step is to prepare for human clinical trials, the twoscientists said. "If we can knock out 70, 80 or 90 percent oftumors without drug accumulation in normal tissues in mice, it islikely that many cancer patients could benefit from this new typeof treatment in the long run," Lacko said. Only cancer and liver cells express HDL receptor Previous studies have shown that cancer cells attract and scavengeHDL by producing high levels of its receptor, SR-B1. As cancercells take in HDL, they grow and proliferate. The only other sitein the body that makes SR-B1 receptor is the liver. Thisselectivity for cancer cells protects normal, healthy cells fromside effects. Previous attempts to deliver siRNA by lipsomes and othernanoparticles have been hampered by toxicity and other concerns.The tiny bits of RNA, which regulate genes in a highly targetedfashion, can't simply be injected, for example. "If siRNA is not in a nanoparticle, it gets broken down andexcreted before it can be effective," Sood said. "HDL is completelybiocompatible and is a safety improvement over other types ofnanoparticles." The team developed a synthetic version of HDL, called rHDL, becauseit's more stable than the natural version. Fewer and smaller tumors, less toxicity Using rHDL as a delivery method has other advantages as well. rHDLhas not shown to cause immunologic responses, helping to minimizepotential side effects, Lacko said, and it exhibits longer time incirculation than other drug formulations or lipoproteins. Also,because SR-B1 is found only in the liver, an rHDL vehicle will helpblock and treat metastasis to that organ. Researchers first confirmed the distribution of SR-B1 and theuptake of rHDL nanoparticles in mice injected with cancer cells.They found that siRNA was distributed evenly in about 80 percent ofa treated tumor. As expected, the nanoparticles accumulated in theliver with minimal or no delivery to the brain, heart, lung, kidneyor spleen. Safety studies showed uptake in the liver did not causeadverse effects. Using siRNA tailored to the individual gene, the researchersseparately shut down the genes STAT3 and FAK in various types oftreatment-resistant ovarian cancer tumors. STAT3 and FAK areimportant to cancer growth, progression and metastasis; however,they also play important roles in normal tissue so targetingprecision is vital. The siRNA/rHDL formulation alone reduced the size and number oftumors by 60 to 80 percent. Combinations with chemotherapy causedreductions above 90 percent. Conventional approaches to target STAT3 have met limited success,Sood said. FAK, which is over expressed in colorectal, breast,ovarian, thyroid and prostate cancers , is particularly aggressive in ovarian cancer and one reason forits poor survival rate. While previous attempts have targeted FAKwith liposomal nanoparticles or small molecule inhibitors, thesemethods are not tumor-specific and are more likely to harm normalcells, the scientists noted. Next Step: Clinical Studies "In order to help expedite the study's progress to a clinicalsetting, we have identified 12 genes as biomarkers for response toSTAT3-targeted therapy," Sood said. "Next, we'll work with theNational Cancer Institute Nanoparticle Characterization Lab todevelop a formulation of the HDL/siRNA nanoparticle for human use." MD Anderson and UNT have applied for a patent for the nanoparticledelivery method. These arrangements are managed by MD Anderson andthe University of North Texas HSC in accordance with institutionalconflict of interest policies. Source: University of Texas M. D. Anderson Cancer Center Additional References Citations. We are high quality suppliers, our products such as Filled Ptfe Products , Teflon Ptfe Sheet for oversee buyer. To know more, please visits Ptfe Teflon Gasket.
Related Articles -
Filled Ptfe Products, Teflon Ptfe Sheet,
|
