The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report ~30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of goldcoated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of ~70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of ~10 −14 m 2 . Because of the thin gold shells with an average thickness of only 2 nm, the r 2 spin-spin magnetic relaxivity is 219 mM −1 s −1 , an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of *Address correspondence to: kpj@che.utexas.edu, FELDMANM@uthscsa.edu. Supporting Information Available: Reproducibility in nanorose size distribution; porosity of dextran in the shells about the iron oxide particle; estimation of number of particles per nanocluster; average optical density spectra in macrophages labeled with nanorose by hyperspectral microscopy; and laser vaporization of macrophages in vitro. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2010 September 22. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy. Keywordsgold; iron oxide; nanocluster; near-infrared; macrophage targeted imaging; MRI; atherosclerosis; cancer Clinical imaging and/or therapy with multifunctional nanoparticles that target specific types of cells has the potential to transform health care in cancer, atherosclerosis, and other diseases. When the nanoparticle diameters are reduced to 20-50 nm, the biological pathways in targeted cells can undergo profound changes. [1][2][3][4][5] Small nanoparticles, the size of small viruses, permeate barriers more rapidly including cell membranes and leaky vasculature in cancers. The efficacy of vaccines may be enhanced with ultrasmall 20 nm nanoparticles that can dif...

This study was designed to test whether nonsteroidal anti-inflammatory medications could reduce the frequency of atrial fibrillation after coronary artery bypass graft surgery. The study was designed as an open-label, randomized trial. Patients undergoing first-time coronary artery bypass graft surgery were considered eligible. Patients with a history of atrial fibrillation, serum creatinine >2.0 mg/dL, on antiarrhythmic treatment, and those undergoing concomitant valvular surgery were excluded. The study was conducted in a single, university-affiliated community hospital. The researchers' role in the study was restricted to randomizing the patients and collecting data. The primary clinical care team made all decisions regarding patient care. One hundred patients were randomized to two groups: one received 30 mg ketorolac intravenously every 6 hours until able to take oral medications, at which point the patients were switched to 600 mg ibuprofen orally three times a day; the other group received conventional treatment. The primary end point of the study was incidence of atrial fibrillation in the immediate postoperative period. Atrial fibrillation occurred in 14 patients (28.6%) in the conventional treatment group vs. five patients (9.8%) in the ibuprofen group (p<0.017). Nonsteroidal anti-inflammatory medications were relatively safe and effective in significantly reducing the incidence of atrial fibrillation after coronary artery bypass graft surgery.

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