Liposomes Loaded with siRNA Stop Growth of Ovarian Tumors

Cancer researchers have developed a method for delivering gene-inhibiting short-interfering RNA (siRNA) in a form readily taken up by the cytoplasm of cancer cells.
Use of siRNA to inhibit genes that promote the rapid growth of cancer cells is of tremendous interest to cancer researchers. The main problem has been how to transport the siRNA oligomers through the membrane of the cancer cell and into the cytoplasm.

Investigators at the University of Texas M.D. Anderson Cancer Center (Houston, USA) inserted siRNA directed against the gene for focal adhesion kinase (FAK) into neutral liposomes prepared from 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). These liposomes, with and without accompanying docetaxel (a commonly used chemotherapeutic agent), were injected into mice that had been implanted with one of three different human ovarian cancer lines. Control animals received injections of liposomes alone or liposomes containing an inert siRNA.

Results published in the August 15, 2006, issue of Clinical Cancer Research revealed that treatment with FAK siRNA-DOPC liposomes (150 µg/kg twice weekly) reduced mean tumor weight by 44-72% in the three cell lines, compared with the control group. Combining the FAK siRNA-DOPC liposomes with docetaxel increased tumor weight reduction to the 94-98% range. The overall effect of the drug treatment was to induce apoptosis among blood vessel cells and to steeply reduce the number of small blood vessels feeding the tumors.

"Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor,” explained senior author Dr. Anil Sood, associate professor of oncology at the University of Texas M. D. Anderson Cancer Center. "The next step for the FAK siRNA-DOPC liposome is toxicity testing. So far it appears to be very well-tolerated, and we hope to develop this approach for clinical use in the future.”



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University of Texas M.D. Anderson Cancer Center