New Report Highlights Promise of Nanotechnology for Cancer, Other Diseases (2007)

WASHINGTON, DC—The March approval of lapatinib for patients with advanced, HER2-positive metastatic breast cancer—to be used in combination with capectabine—has focused attention on the emerging application of nanotechnology in cancer treatment. Lapatinib, a targeted new molecular entity that deprives cancer cells of growth signals, is an example of a practical application of that technology, which is the measurement, prediction, and construction of materials that are very, very small, on the scale of atoms and molecules. A nanometer is one-billionth of a meter; the width of a human hair is about 80,000 nanometers. The future of nanotechnology was the topic of a report released at a news briefing here by the Project on Emerging Nanotechnologies (PEN) (www.nanotechproject.org) of the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts. The report, NanoFrontiers: Visions for the Future of Nanotechnology, grew out of a workshop in Washington in February 2006 and was sponsored by PEN along with the National Science Foundation and the National Institutes of Health.FigureFirst ‘Nanomedicine’ The first “nanomedicine,” the report notes, was Abraxane, made by loading paclitaxel into nanoparticles of the protein albumin; the formulation was approved in January 2005 as a less toxic way to treat metastatic breast cancer. Now there are about 130 nanomedicines in the pipeline—the first wave likely to be mostly reformulations of existing drugs. $1 Billion Today, the pharmaceutical industry already sells more than $1 billion worth of drugs coated with nanoparticles or encapsulated in nanoscale packaging, according to PEN. In addition to Abraxane, nano-enabled drugs now in use include Doxil, doxorubicin HCl liposome-borne treatment for metastatic ovarian cancer. Scientists are testing novel methods of drug delivery—nanocapsules, nanotubes, buckyballs, and dendrimer starbursts—for targeting and steering chemotherapy agents to cancerous tumors. Samuel I. Stupp, PhD, Board of Trustees Professor of Materials Science, Chemistry, and Medicine at Northwestern University, is working with breast cancer cell lines to create “killer nanostructures” (pro-apoptotic nanostructures) that can trigger apoptosis in cancer cells. “These go to the mitochondria of breast cancer cells and the cells commit suicide,” Dr. Stupp, who participated in the nanofrontier workshop that led to the new report, said at the news briefing. He is also working on a liposome nanostructure chemotherapy-delivery system, which he said is “like a Trojan horse” in the stealth of its effectiveness. Dr. Stupp receives grant support from a number of NIH institutes, including the NCI. ‘Nanotools’ In addition to the promise of new drugs, nanotechnology'S “nanotools” hold remarkable promise for imaging tissues and analyzing blood, according to the new report. Already being tested is a diagnostic kit that uses gold nanoparticles to detect prostate cancer so early that the numbers of protein biomarkers in the blood are still very low. Nanoparticles are being used not only to detect cancer cells but also atherosclerotic plaque and other disease processes, said Lynn D. Hudson, PhD, Director of the Office of Science Policy Analysis in the NIH Director'S Office of Science Policy. “If we can get even higher resolution to tag and then look at individual nano-labeled proteins dancing around inside of a cell, we'll get the kind of information about the intricate interactive complexities of our bodies that now we can only guess at,” said Dr. Hudson, who, like Dr. Stupp, participated in the nanofrontier workshop that led to the new report and in the news briefing. “We can start to unpack the engineering principles used by living cells to build molecules and molecular complexes, organelles, cells, and tissues.” It should be possible to “learn how mother nature managed to come up with the best molecular motors and copy her design using nanotechnology to ultimately engineer new devices and structures for tissue repair and disease cures,” she added. Nano-Predictions PEN predicts that nano-imaging: Will have greater specificity at the level of individual cells. Will allow for earlier detection and increase the odds of effective treatment before tumors metastasize…Will be less invasive but yield more definitive results. Will be faster and simpler, presenting more options for rapid, point-of-care diagnostics. The PEN report is another in a growing number of nanotechnology activities in the public and private sectors. At the impetus of NIH Director Elias Zerhouni, MD, the NIH established a Trans-NIH Nanotechnology Task Force a year ago. That umbrella task force will develop an NIH-wide scientific and policy vision for nanotechnology and consider its legal and societal implications, among other endeavors, Dr. Hudson noted. “The growth of support for nano research at NIH has ramped up considerably, going from an investment of $40 million in fiscal year 2001 to $190 million in fiscal year 2006,” she noted. “In the past six years, our actual funding levels have exceeded official projections. NIH currently supports eight Nanomedicine Development Centers from a common fund. In addition, a number of institutes have made substantial financial commitments.” These include NCI, which funds the Alliance for Nanotechnology in Cancer, NIH'S largest single nanotechnology program. This program—budgeted at $35 million to $40 million a year—includes eight Centers of Cancer Nanotechnology Excellence and 12 Nanotechnology Platform Development Partnerships.Figure: Samuel I. Stupp, PhD, is working with breast cancer cell lines to create “killer nanostructures” (pro-apoptotic nanostructures), that can trigger apoptosis in cancer cells. He is also working on a liposome nanostructure chemotherapy-delivery system, which he compared to a Trojan horse in the stealth of its effectiveness.This NCI initiative also includes the Nanotechnology Characterization Laboratory, in partnership with the FDA and the National Institute of Standards and Technology (NIST), whose task is to standardize the preclinical characterization of nanomaterials intended for cancer diagnostics and therapeutics, and provide the infrastructure for research on nanomaterials' environmental, health, and safety implications. Constraints & Challenges At the nanotechnology news briefing, NIH'S Lynn D. Hudson, PhD, characterized the potential challenges for this science of the very small as encompassing the following: The need to figure out the best way to educate a new generation of interdisciplinary translational scientists who are skilled in work on the nanoscale. “This is easier said than done,” she said, citing Dr. Samuel Stupp of the Institute of BioNanotechnology in Medicine at Northwestern University as an example of a researcher who can bridge different worlds. The need to ensure that scientists develop adequate methods to systematically assess the environmental, health, safety, and societal impact of materials at the nanoscale. In fiscal year 2006 NIH invested more than $5.2 million into assessing the health effects of nanotechnologies, Dr. Hudson noted. The National Institute of Environmental Health Sciences, under the umbrella of the Trans-NIH Nanotechnology Task Force, is leading a Health Implications Work Group to consider not only unintentional exposures to nanomaterials but also intentional exposures to nanodiagnostics and therapeutics. The National Toxicology Program is leading the Nanotechnology Safety Initiative, which will undertake evaluations on specific nanoscale materials, including quantum dots, metal oxides, and carbon fullerenes. The need to have the foresight to fully communicate with all stakeholders about the parameters, threats, and promise of nanotechnology, along with the vision to enlist the support of the United States and its colleagues abroad, to make sure that essential nanotechnology research goes forward and does not get stalled. The need for much closer collaboration among scientists concerned about the economic consequences, safety and benefits of this emerging science. Figure: Lynn D. Hudson, PhD, Director of the Office of Science Policy Analysis in the NIH Director'S Office of Science Policy, said the NanoFrontiers report represents “a good first nanostep.”More Info Further information about the Nanofrontiers report can be found at www.nanotechproject.org/114 Advantages of ‘Nano-Enhanced’ Drugs Nano-enhanced drugs have the following key advantages, the PEN report notes: They can be targeted and customized to the individual patient, with fewer side effects and can be engineered to slip through the blood-brain barrier, mucus, or other obstacles. They allow for expanded options for administration, such as nasal, dermal, oral, and ocular. They allow for combined detection and treatment approaches, a kind of “seek and destroy” therapy followed by inside-the-body monitoring of the patient'S response.