Nanotechnology and Oncology Workshop Summary (2011) / Chapter Skim
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3 Research and Development of New Cancer Nanomedicines - Challenges and Solutions
3 Research and Development of New Cancer Nanomedicines - Challenges and Solutions
Pages 25-40
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This chapter discusses challenges in basic biology (including biomarker discovery) , strategies for improving nanoparticle targeting effectiveness and efficiency, design complexity of nanomaterials for medical applications, the transition from laboratory to manufacturing, and bridging multiple disciplines.
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Hawk noted, and improved sensitivity and specificity of the technologies used to detect preinvasive neoplasia or early-stage cancer. Also needed are ways to identify populations at risk for prevention studies, and to identify meaningful endpoints for cancer prevention trials.
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We have to join together the fields and know what we did -- what worked and what didn't work -- and then we'll go forward along the road more quickly." STRATEGIES FOR IMPROVING NANOPARTICLE TARGETING EFFECTIVENESS AND EFFICIENCY Workshop speakers and participants discussed the need for and strategies for improving targeting capabilities of nanotherapeutics and imaging agents. One key question that needs to be addressed is whether cancertargeting molecules are reliably attached to the nanoparticles, Dr.
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(c) Active binding of albumin-drug complex by SPARC in tumor, leading to paclitaxel-induced tumor cell apoptosis.
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Ferrari echoed by saying that within oncology "the low-hanging fruits have been taken care of, and unless we come up with a true paradigm change, it is not going to be that simple. So don't keep it simple." Dr.
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Dr. Libutti added that one major concern FDA raised at his IND meeting for the nanoTNF medicine he created was that the particles should be uniform in size and substance when his lab characterized them.
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Dr. Ferrari added that it is hard to find institutional setups that enable such multidisciplinary, team research, while at the same time enabling researchers to pursue their own individual careers.
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To scale up and produce large quantities, he then uses a "roll to roll" process similar to what is used in the film industry. With this process, the mold, in sheet form, is matched to a delivery sheet that is used to form the actual nanomedicines, which are peeled away from the mold sheet using a harvesting film with an adhesive on it (see figure below)
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One aspect of his research involves modifying the deformability of the nanopar ticles he engineers because there is evidence that the deformability of metastatic cancer cells enables them to metastasize (Suresh, 2007)
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The Alliance is focused on team science and has multiple interagency collaborations, including those with the National Institute of Standards and Technology, the Food and Drug Administration, the National Institute of Environmental Health Sciences and the Environmental Protection Agency. A major goal for the NCI Alliance for Nanotechnology in Cancer is to quicken the pace of nanotechnology discovery and development efforts, and to lower the barriers to commercialize these advances for the benefit of cancer patients.
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By balancing structured directives with investigator-initiated research, the CCNEs bring together the interdisciplinary teams from existing NCI resources and provide the infrastructure necessary to develop and translate nanotechnology advances to the clinic. Multidisciplinary Research Training and Team Development The Alliance supports training and career development initiatives to establish integrated teams of cancer researchers, epidemiologists, engineers, and others to approach the fundamental challenges of cancer using cancer biology, physical science skills, and the knowledge base of nanotechnology.
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, the Nanotechnology Characterization Laboratory is developing data that will facilitate standards for nanoscale devices, and facilitate regulatory review of these products prior to market release. Using standardized methods, the NCL characterizes the physical and chemical parameters of nanoparticles and conducts structure–activity relationships studies that aid assessments of biocompatibility.
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The Nanosafety Lab also makes recommendations regarding regulation of research and industrial activities on nanotechnology, fosters international nanotechnology collaborations and standards, and aids safety assessment for nanotechnology industry by developing assessment methods and procedures, and identifying toxic classes of nanomaterials. The Nanosafety Lab engages 16 institutions and universities in China in the study of nanosafety issues, and receives its support from the Chinese government, the National Natural Science Foundation of China (NSFC)
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. AFM = atomic force microscopy; CE = capillary electrophoresis; FFF = field flow fractionation; GC = gas chromatography; HPLC = high-performance liquid chromatography; IR = infrared spectroscopy; NMR = nuclear magnetic resonance spectroscopy; PAGE = polyacrylamide gel electrophoresis; SEC = size exclusion chromatography; SEM = scanning electron microscopy; TEM = transmission electron microscopy; UV-Vis = ultraviolet–visible spectroscopy.
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Kristen Kulinowski, senior faculty fellow in the Department of Chemistry at Rice University and Director for External Affairs for the Center for Biological and Environmental Nanotechnology.
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