TY - JOUR T1 - Antiandrogen Gold Nanoparticles Dual-Target and Overcome Treatment Resistance in Hormone-Insensitive Prostate Cancer Cells JF - Bioconjugate Chemistry Y1 - 2012 A1 - Dreaden, E. C. A1 - Gryder, B. E. A1 - Austin, Lauren A1 - Defo, B. A. T. A1 - Hayden, S. C. A1 - Pi, M. A1 - Quarles, L. D. A1 - Oyelere, A. K. A1 - El-Sayed, M. A. AB - prostate cancer is the most commonly diagnosed cancer among men in the developed countries.(1) One in six males in the U.S.(2) and one in nine males in the U.K.(3) will develop the disease at some point during their lifetime. Despite advances in prostate cancer screening, more than a quarter of a million men die from the disease every year(1) due primarily to treatment-resistance and metastasis. Colloidal nanotechnologies can provide tremendous enhancements to existing targeting/treatment strategies for prostate cancer to which malignant cells are less sensitive. Here, we show that antiandrogen gold nanoparticles-multivalent analogues of antiandrogens currently used in clinical therapy for prostate cancer-selectively engage two distinct receptors, androgen receptor (AR), a target for the treatment of prostate cancer, as well as a novel G-protein coupled receptor, GPRC6A, that is also upregulated in prostate cancer. These nanoparticles selectively accumulated in hormone-insensitive and chemotherapy resistant prostate cancer cells, bound androgen receptor with multivalent affinity, and exhibited greatly enhanced drug potency versus monovalent antiandrogens currently in clinical use Further, antiandrogen gold nanoparticles selectively stimulated GPRC6A with multivalent affinity, demonstrating that the delivery of nanoscale antiandrogens can also be facilitated by the transmembrane receptor in order to realize increasingly selective, increasingly potent therapy for treatment-resistant prostate cancers. VL - 23 SN - 1043-1802 N1 - Times Cited: 0Dreaden, Erik C. Gryder, Berkley E. Austin, Lauren A. Defo, Brice A. Tene Hayden, Steven C. Pi, Min Quarles, L. Darryl Oyelere, Adegboyega K. El-Sayed, Mostafa A. M3 - 10.1021/bc300158k ER - TY - JOUR T1 - Detecting and Destroying Cancer Cells in More than One Way with Noble Metals and Different Confinement Properties on the Nanoscale JF - Accounts of Chemical Research Y1 - 2012 A1 - Dreaden, E. C. A1 - El-Sayed, M. A. AB - Today, 1 in 2 males and 1 in 3 females in the United States will develop cancer at some point during their lifetimes, and 1 in 4 males and 1 in 5 females in the United States will die from the disease. New methods for detection and treatment have dramatically improved dancer care in the United States. However, as improved detection and increasing exposure to carcinogens has led to higher rates of cancer incidence, dinidans and researchers have not balanced that increase with a similar decrease in cancer mortality rates. This mismatch highlights a dear and urgent need for increasingly potent and selective methods with which to detect and treat cancers at their earliest stages. Nanotechnology, the use of materials with structural features ranging from 1 to 100 nm in size, has dramatically altered the design, use, and delivery of cancer diagnostic and therapeutic agents. The unique and newly discovered properties of these structures can enhance the specificities with which biomedical agents are delivered, complementing their efficacy or diminishing unintended side effects. Gold (and silver) nanotechnologies afford a particularly unique set of physiological and optical properties which can be leveraged In applications ranging from in vitro/vivo therapeutics and drug delivery to imaging and diagnostics, surgical guidance, and treatment monitoring. Nanoscale diagnostic and therapeutic agents have been in use since the development of micellar nanocarriers and polymer drug nanoconjugates in the mid-1950s, liposomes by Bangham and Watkins in the mid-1960s, and the introduction of polymeric nanoparticles by Langer and Folkman in 1976. Since then, nanoscale constructs such as dendrimers, protein nanoconjugates, and inorganic nanoparticles have been developed for the systemic delivery of agents to specific disease sites. Today, more than 20 FDA-approved diagnostic or therapeutic nanotechnologies are in clinical use with roughly 250 others in clinical development The global market for nano-enabled medical technologies is expected to grow to $70-160 billion by 2015, rivaling the current market share of biologics worldwide. In this Account, we explore the emerging applications of noble metal nanotechnologies in cancer diagnostics and therapeutics carried out by our group and by others. Many of the novel biomedical properties associated with gold and silver nanoparticles arise from confinement effects: (i) the confinement of photons within the particle which can lead to dramatic electromagnetic scattering and absorption (useful in sensing and heating applications, respectively); (ii) the confinement of molecules around the nanoparticle (useful in drug delivery); and (iii) the cellular/subcellular confinement of particles within malignant cells (such as selective, nuclear-targeted cytotoxic DNA damage by gold nanoparticles). We then describe how these confinement effects relate to specific aspects of diagnosis and treatment such as (i) laser photothermal therapy, optical scattering microscopy, and spectroscopic detection, (ii) drug targeting and delivery, and (iii) the ability of these structures to act as intrinsic therapeutic agents which can selectively perturb/inhibit cellular functions such as division. We intend to provide the reader with a unique physical and chemical perspective on both the design and application of these technologies in cancer diagnostics and therapeutics. We also suggest a framework for approaching future research in the field. VL - 45 SN - 0001-4842 N1 - Times Cited: 0Dreaden, Erik C. El-Sayed, Mostafa A.Si M3 - 10.1021/ar2003122 ER - TY - JOUR T1 - The golden age: gold nanoparticles for biomedicine JF - Chemical Society Reviews Y1 - 2012 A1 - Dreaden, E. C. A1 - Alkilany, A. M. A1 - Huang, X. H. A1 - Murphy, C. J. A1 - El-Sayed, M. A. AB - Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of 'gilding the (nanomedicinal) lily', but that a new 'Golden Age' of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references). VL - 41 SN - 0306-0012 N1 - Times Cited: 54Dreaden, Erik C. Alkilany, Alaaldin M. Huang, Xiaohua Murphy, Catherine J. El-Sayed, Mostafa A. M3 - 10.1039/c1cs15237h ER - TY - JOUR T1 - Small Molecule-Gold Nanorod Conjugates Selectively Target and Induce Macrophage Cytotoxicity towards Breast Cancer Cells JF - Small Y1 - 2012 A1 - Dreaden, E. C. A1 - Mwakwari, S. C. A1 - Austin, Lauren A1 - Kieffer, M. J. A1 - Oyelere, A. K. A1 - El-Sayed, M. A. VL - 8 SN - 1613-6810 N1 - Times Cited: 0Dreaden, Erik C. Mwakwari, Sandra C. Austin, Lauren A. Kieffer, Matthew J. Oyelere, Adegboyega K. El-Sayed, Mostafa A. M3 - 10.1002/smll.201200333 ER -