The nanoscale, tiny by any definition, ranges from approximately 1 to 100 nanometers; for reference, a human hair is roughly 80,000 nanometers in width. Nanotechnology or molecular engineering at the nanoscale promises great benefits to molecular medicine. The merger of these fields necessitates the types of interdisciplinary collaborations that foster ingenuity. Nanotechnology offers new options for drug delivery and nanomaterials can enhance the development of medical imaging modalities. Nanoscale sensors offer impressive improvements in sensitivity for disease biomarkers, and nanoscale bioengineering offers a multitude of opportunities to study and treat disease with synthetic biomolecules or via tissue regeneration.
The unique physical, chemical and biological properties of nanomaterials also raise questions about safety and therefore offer new challenges to regulatory bodies. In 2006, the US Food and Drug Administration (FDA) initiated the Nanotechnology Task Force to assess the state of the science and to evaluate regulatory issues; the report produced by this group is available for download via the website of the FDA (http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/NanotechnologyTaskForceReport2007/default.htm). Around the same time, the European Medicines Agency (EMEA) created the Innovation Task Force (ITF; http://www.emea.eu.int/htms/human/itf/itfintro.htm) to ensure coordination and regulatory competence for emerging technologies. Although regulatory agencies continue to monitor developments in nanotechnology and policies surrounding the use of nanomaterials will continue to evolve, both the FDA and EMEA encourage scientists and manufacturers to communicate with them early in the development process for products using these materials.
Against this backdrop, Trends in Molecular Medicine is pleased to present a special issue devoted to Nanomedicine. Given the breadth of molecular medicine and the multitude of areas where nanotechnology is impacting this field, the collection of articles in this issue reflects merely a sample of the exciting advances in this arena.
Molecular imaging, a powerful tool for the diagnosis and monitoring of diseases including cancer, cardiovascular disease and neurological disorders, is an area where nanotechnology is already impacting medicine. Importantly, nanomaterials increase the sensitivity of molecular imaging modalities creating opportunities for clinicians to detect disease earlier. In this issue, Cho and colleagues review advances in the development of inorganic particle-based contrast agents that promise to improve existing imaging modalities and create new options for multimodal technologies. Although iron oxide nanoparticles are already in clinical use, this review offers an overview of additional particles in preclinical development, and how various surface modifications can impact the behavior of these molecules in circulation and enhance their functionality.
He and colleagues review advances in near-infrared (NIR) fluorescent nanoprobes and the advantages they offer over conventional NIR probes and other fluorescent dyes as well as different modes of targeting NIR fluorescence to tumors, including passive targeting, active targeting and the generation of activatable probes. These developments, among others, are moving this technology rapidly towards the clinic; however, the authors conclude by highlighting challenges that must be overcome for this work to translate into improved patient care.
In addition to serving as molecular imaging agents, nanoparticles can carry cargo, such as small-molecule drugs for cancer treatment. Chen reviews nanocarriers that can affect features of small-molecule drugs making them more suitable for clinical use, improving their efficacy and reducing their toxicity. Chen also reviews mechanisms for achieving controlled release of agents in tumors; she further highlights targeting tumor metastasis as a major area of ongoing research, identifying important questions that remain.
Nanotechnology has also improved the sensitivity of biosensors, including those used by patients with diabetes to monitor their blood glucose levels. Cash and Clark review the ways nanomaterials are improving properties of available sensors and allowing the fabrication of new sensors. The authors also review the emergence of “smart tattoos”, temporary sensors in the skin that change color in response to fluctuations in glucose levels, that could replace the invasive finger-prick devices currently used by patients and provide around-the-clock monitoring, which should empower patients to better manage their disease.
Bioengineering with nanomaterials is opening new doors for research, treatment and regeneration. In this issue, Luthi and colleagues review strategies to treat atherosclerosis by affecting levels of circulating cholesterol. A common goal of current preventative therapies in heart disease is to increase the levels of high-density lipoproteins (HDLs), a heterogeneous collection of lipoprotein cholesterol transporters. Emerging evidence indicates that disparate HDL species are not biologically equivalent. The authors suggest that nanotechnology offers the opportunity to synthesize well-defined and disparate HDL species so their biological properties can be systematically studied, potentially paving the way for therapies with synthetic HDLs or improving imaging options for detecting and monitoring atherosclerotic plaques.
One common outstanding question identified by authors in this issue is: how do the physical and chemical properties of nanoparticles influence biodistribution and toxicity? Cho and colleagues suggest this question will have to be addressed on a particle-by-particle basis; however, because this appears to be such an important issue, which will affect the use of the various nanoparticles in humans, we hope these reviews will inspire new efforts to address this important question.
Finally, Trends in Molecular Medicine would like to thank all of the contributors to this special issue, the authors and the referees, for making this issue possible, and we hope you enjoy the articles as much as we did.