by Gloria J. Kim and Shuming Nie* Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 101 Woodruff Circle Suite 2001, Atlanta, GA 30322, USA *E-mail: snie@emory.edu Significant progress has been made in the development of new agents against cancer and new delivery technologies. Proteomics and genomics continue to uncover molecular signatures that are unique to cancer. Yet, the major challenge remains in targeting and selectively killing cancer cells while affecting as few healthy cells as possible. Nanometer-sized particles have novel optical, electronic, and structural properties that are not available from either individual molecules or bulk solids. When linked with tumor-targeting moieties, such as tumor-specific ligands or monoclonal antibodies, these nanoparticles can be used to target cancer-specific receptors, tumor antigens (biomarkers), and tumor vasculatures with high affinity and precision. Conventional cancer therapy and diagnostics involves the application of catheters, surgery, biopsy, chemotherapy, and radiation. Most current anticancer agents do not greatly differentiate between cancerous and normal cells. This leads to systemic toxicity and adverse effects. Consequently, the systemic application of these drugs often causes severe sideeffects in other tissues (e.g. bone marrow suppression, cardiomyopathy, and neurotoxicity), which greatly limits the maximal allowable dose of the drug. In addition, rapid elimination and widespread distribution into nontargeted organs and tissues requires the administration of a drug in large quantities, which is uneconomical and is often complicated because of nonspecific toxicity. Nanotechnology could offer a less invasive alternative, enhancing the life expectancy and quality of life of the patient. The diameter of human cells spans 10-20 μm. The size of cell organelles ranges from a few nanometers to a few hundred nanometers. Nanoscale devices can readily interact with biomolecules on the cell surface and within the cells in a noninvasive manner, leaving the behavior and biochemical properties of those molecules intact. In their ‘mesoscopic’ size range of 10-100 nm in diameter, nanoparticles have more surface areas and functional groups that can be linked to multiple optical, radioisotopic, or magnetic diagnostic and therapeutic agents. When linked with tumor-targeting ligands such as monoclonal antibodies, these nanoparticles can be used to target tumor antigens (biomarkers), as well as tumor vasculatures with high affinity and specificity. In this cancer nanotherapy ISSN:1369 7021 © Elsevier Ltd 2005 Targeted August 2005 28