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Novel 3-D cell culture model shows selective tumor uptake of nanoparticles
August 23, 2007A nanoparticle drug delivery system designed for brain tumor therapy has shown promising tumor cell selectivity in a novel cell culture model devised by University of Nottingham scientists. The project, conducted jointly in the Schools of Pharmacy, Biomedical Sciences and Human Development, will be featured in the September issue of the Experimental Biology and Medicine.
Therapy for brain cancers is particularly difficult for a number of reasons, including getting sufficient drug to the tumor and selectivity of drug action. "We are working on a number of new therapeutic approaches using nanoparticle drug delivery systems explained Dr Martin Garnett, Associate Professor of drug delivery at the School of Pharmacy, however, understanding and developing these systems requires suitable models for their evaluation."
The nanoparticles used in this study were prepared from a novel biodegradable polymer poly(glycerol adipate). The polymer has been further modified to enhance incorporation of drugs and make the nanoparticles more effective.
"The interaction of tumor cells with brain cells varies between different tumors and different locations within the brain explained Dr Terence Parker, Associate Professor in the School of Biomedical Sciences. Using 3-dimensional culture models is therefore important in ensuring that the behavior of cells in culture is similar to that seen in real life."
The work was mainly carried out by graduate student Weina Meng who formulated the fluorescently labeled nanoparticles and studied them in a variety of tumor and brain cell cultures. Her early studies showed faster uptake of nanoparticles into tumor cell cultures than normal brain cell cultures grown separately. This selectivity was only seen in 3-dimensional cultures and was the driving force to develop a more complex and representative model.
Tumor cell aggregates have been used as cell culture models of cancer cells for many years. Similarly thin brain slices from newborn rats can be cultured for weeks and are an important tool in brain biology. In the cell co-culture model now reported, these two techniques have been brought together for the first time. Brain tumor cell aggregates were labeled with fluorescent iron microparticles and grown on normal newborn rat-brain tissue slices. The double cell labeling technique allowed investigation of tumor cell invasion into brain tissue by either fluorescence or electron microscopy from the same samples. Using these techniques the tumor aggregates were found to invade the brain slices in a similar manner to tumors in the body. Having developed the model then the tumor selective uptake of nanoparticles was demonstrated in the co-culture.
The collaboration on this project has been nurtured by Professor David Walker of the School of Human Development who co-founded the Children's Brain Tumor Research Group at Nottingham. "Understanding the biology of tumors is important if we are to develop effective new treatments said Professor Walker. This work demonstrates how close co-operation between disciplines can help to push forward ideas which could lead to new clinical therapies."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, agrees with Professor Walker. Dr. Goodman stated "The convergence of cancer cell biology and nanoscience, exemplified by this study, holds great promise for the future of brain tumor therapy." Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.
Society for Experimental Biology and Medicine
"The interaction of tumor cells with brain cells varies between different tumors and different locations within the brain explained Dr Terence Parker, Associate Professor in the School of Biomedical Sciences. Using 3-dimensional culture models is therefore important in ensuring that the behavior of cells in culture is similar to that seen in real life."
The work was mainly carried out by graduate student Weina Meng who formulated the fluorescently labeled nanoparticles and studied them in a variety of tumor and brain cell cultures. Her early studies showed faster uptake of nanoparticles into tumor cell cultures than normal brain cell cultures grown separately. This selectivity was only seen in 3-dimensional cultures and was the driving force to develop a more complex and representative model.
Tumor cell aggregates have been used as cell culture models of cancer cells for many years. Similarly thin brain slices from newborn rats can be cultured for weeks and are an important tool in brain biology. In the cell co-culture model now reported, these two techniques have been brought together for the first time. Brain tumor cell aggregates were labeled with fluorescent iron microparticles and grown on normal newborn rat-brain tissue slices. The double cell labeling technique allowed investigation of tumor cell invasion into brain tissue by either fluorescence or electron microscopy from the same samples. Using these techniques the tumor aggregates were found to invade the brain slices in a similar manner to tumors in the body. Having developed the model then the tumor selective uptake of nanoparticles was demonstrated in the co-culture.
The collaboration on this project has been nurtured by Professor David Walker of the School of Human Development who co-founded the Children's Brain Tumor Research Group at Nottingham. "Understanding the biology of tumors is important if we are to develop effective new treatments said Professor Walker. This work demonstrates how close co-operation between disciplines can help to push forward ideas which could lead to new clinical therapies."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, agrees with Professor Walker. Dr. Goodman stated "The convergence of cancer cell biology and nanoscience, exemplified by this study, holds great promise for the future of brain tumor therapy." Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.
Society for Experimental Biology and Medicine
Tumor Cell Current Events and Tumor Cell News RSSNew Notre Dame study provides insights into the molecular basis of tumor cell behavior
A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.
Outfoxing pox: Developing a new class of vaccine candidates
In the annals of medicine, Edward Jenner's 1796 vaccination of a young boy against smallpox, using fluid from cowpox blisters, remains a landmark case. In a new study, Kathryn Sykes, a researcher at Arizona State University's Biodesign Institute and her colleagues have taken a fresh look at cowpox.
M. D. Anderson examines use of toad venom in cancer treatment
Huachansu, a Chinese medicine that comes from the dried venom secreted by the skin glands of toads, has tolerable toxicity levels, even at doses eight times those normally administered, and may slow disease progression in some cancer patients, say researchers from The University of Texas M. D. Anderson Cancer Center.
Novel 'on-off switch' mechanism stops cancer in its tracks
A tiny bit of genetic material with no previously known function may hold the key to stopping the spread of cancer, researchers at Yale School of Medicine and Sichuan University in Chengdu, China report in two papers in the September 7-11 issue of Proceedings of the National Academy of Sciences.
Lung cancer suppresses miR-200 to invade and spread
Primary lung cancer shifts to metastatic disease by suppressing a family of small molecules that normally locks the tumor in a noninvasive state, researchers at The University of Texas M. D. Anderson Cancer Center report in the Sept. 15 edition of Genes and Development.
New method monitors early sign of oxidative stress in cancer
The growth of cancerous tumors is fueled, at least in part, by the buildup of free radicals-highly reactive oxygen-containing molecules.
Mayo Clinic Researchers Find That Protein Believed to Protect Against Cancer Has a Mr. Hyde Side
In a biological rendition of fiction's Strange Case of Dr. Jekyll and Mr. Hyde, researchers from the Mayo Clinic campus in Florida and Harvard Medical School have found that a protein thought to protect against cancer development can actually spur the spread of tumors.
U-Iowa improves delivery of cancer-fighting molecules
Small interfering RNA (siRNA), a type of genetic material, can block potentially harmful activity in cells, such as tumor cell growth. But delivering siRNA successfully to specific cells without adversely affecting other cells has been challenging.
First compound that specifically kills cancer stem cells found
The cancer stem cells that drive tumor growth and resist chemotherapies and radiation treatments that kill other cancer cells aren't invincible after all.
Estrogen-Dependent Switch Tempers Killing Activity of Immune Cells
The sex hormone estrogen tempers the killing activity of a specific group of immune cells, the cytotoxic T cells (CTLs), which are known to attack tumor cells and cells infected by viruses.
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