The Lankenau Institute for Medical Research (LIMR) announced that in collaboration with the Massachusetts Institute of Technology (MIT) they have performed preclinical proof-of- principle studies showing how nanotechnology can be used to enhance gene therapy for cancer. The results of the study, led by Janet Sawicki, Ph.D. at LIMR and Robert Langer, Ph.D. and Daniel Anderson, Ph.D. at MIT, were reported as a cover article in a recent issue of the Proceedings of the National Academy of Sciences.
This advance offers an alternative method of gene therapy that has advantages over earlier technology. The nanotechnology-based approach used by the researchers has minimal toxic side effects to normal cells. Moreover, it does not rely upon recombinant viruses, the use of which has been questioned recently due to the serious adverse effects they can have in some patients. Such problems have prompted researchers to find alternative methods for delivering gene therapy.
Dr. Sawicki is an expert in preclinical studies of gene therapy for prostate cancer, and she is excited about the success of the current approach. In this study, the MIT group identified a polymer termed C32 that the Lankenau group demonstrated was capable of delivering genes to cancer cells more efficiently and with less toxicity than other polymers that have been tested in the field to date. C32 works by condensing the DNA in a gene and allowing the resulting nanoparticles that are formed to enter cells through a process called endocytosis. Therapeutic genes delivered to cells in this manner are able to drive cellular production of a gene-encoded protein through normal processes.
"By genetically engineering the normal diphtheria toxin gene, we created a toxin that would be produced only in prostate cells," explained Dr. Sawicki. "When we injected prostate tumors in animals with C32 nanoparticles, tumor growth was suppressed or reversed, relative to untreated tumors." As part of their study, the researchers discovered that C32 nanoparticles deliver DNA very efficiently to tumor cells, but very poorly to healthy muscle cells. This feature may help safeguard the healthy tissue surrounding tumors, offering a significant improvement over currently available therapies, which tend to damage the healthy tissue near the tumor.
In future work, the LIMR and MIT researchers aim to expand their work to test whether this nanotechnology can be adapted for a non-radioactive type of brachytherapy, a practice that has grown in popularity to treat localized prostate cancer, including at Lankenau Hospital. They also aim to explore whether nanoparticles can be delivered intravenously to attack metastatic tumor cells, which are found throughout the body in advanced stages of cancer.
According to the American Cancer Society, cancer has surpassed heart disease as the leading killer of Americans younger than 85. In 2005, 232,090 men will be diagnosed with prostate cancer and 30,350 men will die from the disease. Research such as Dr. Sawicki's can lead to treatments that will get rid of the cancer completely, leaving healthy cells untouched. In addition, this type of treatment reduces, and possibly eliminates, the number of unpleasant side effects associated with prostate cancer treatment.
http://www.limr.org/mlh/hprof/limr/article_3611.asp
