We report a one-pot chemical approach for the synthesis of highly monodisperse colloidal nanophosphors displaying bright upconversion luminescence under 980 nm excitation. This general method optimizes the synthesis with initial heating rates up to 100°C∕ minute generating a rich family of nanoscale building blocks with distinct morphologies (spheres, rods, hexagonal prisms, and plates) and upconversion emission tunable through the choice of rare earth dopants. Furthermore, we employ an interfacial assembly strategy to organize these nanocrystals (NCs) into superlattices over multiple length scales facilitating the NC characterization and enabling systematic studies of shape-directed assembly. The global and local ordering of these superstructures is programmed by the precise engineering of individual NC's size and shape. This dramatically improved nanophosphor synthesis together with insights from shape-directed assembly will advance the investigation of an array of emerging biological and energy-related nanophosphor applications.doped nanocrystals | superlattice | lanthanides | luminescence R ecent advances in synthesis and controlled assembly of monodisperse colloidal nanocrystals (NCs) into superlattice structures have enabled their applications in optics (1), electronics (2), magnetic storage (3), etc. Single-and multicomponent superlattices composed of spherical NCs are increasingly studied and a rich family of structures is now accessible (4, 5), where the electronic and magnetic interactions between the constituents gives rise to new cooperative properties (6, 7). New synthetic approaches are yielding nonspherical NCs with physical properties unobtainable by simply tuning the size of the spheres (8-11), providing an even broader array of nanoscale building blocks. The size and shape dependence of NC's biological activity (12, 13) and toxicity (14) is also of intense interest. However, the challenge of precisely controlling particle shape while maintaining uniformity in size and surface functionality has limited studies of NC environmental health and safety just as it has hindered efforts to organize anisotropic building blocks and to establish methods to capture their unique properties in NC superlattice thin films.Lanthanide-doped nanophosphors are an emerging class of optical materials (15). These NCs often possess "peculiar" optical properties [e.g., quantum cutting (16) and photon upconversion (17)], allowing the management of photons that could benefit a variety of areas including biomedical imaging (18, 19) and therapy (20), photovoltaics (16, 21), solid state lighting (22), and display technologies (23). Colloidal upconversion nanophosphors (UCNPs) are capable of converting long-wavelength near-infrared excitation into short-wavelength visible emission through the long-lived, metastable excited states of the lanthanide dopants (24). In contrast to the Stokes-shifted emissions from semiconductor NCs or organic fluorophores and the multiphoton process employing fluorescent dyes, UCNPs offer several ...

Progress in nanocrystal synthesis and self-assembly enables the formation of highly ordered superlattices. Recent studies focused on spherical particles with tunable attraction and polyhedral particles with anisotropic shape, and excluded volume repulsion, but the effects of shape on particle interaction are only starting to be exploited. Here we present a joint experimental-computational multiscale investigation of a class of highly faceted planar lanthanide fluoride nanocrystals (nanoplates, nanoplatelets). The nanoplates self-assemble into long-range ordered tilings at the liquid-air interface formed by a hexane wetting layer. Using Monte Carlo simulation, we demonstrate that their assembly can be understood from maximization of packing density only in a first approximation. Explaining the full phase behaviour requires an understanding of nanoplate-edge interactions, which originate from the atomic structure, as confirmed by density functional theory calculations. Despite the apparent simplicity in particle geometry, the combination of shape-induced entropic and edge-specific energetic effects directs the formation and stabilization of unconventional long-range ordered assemblies not attainable otherwise.

We report a group of optical imaging probes, comprising upconverting lanthanide nanoparticles (UCNPs) and polyanionic dendrimers. Dendrimers with rigid cores and multiple carboxylate groups at the periphery are able to tightly bind to surfaces of UCNPs pretreated with NOBF 4 , yielding stable, water-soluble, biocompatible nanomaterials. Unlike conventional linear polymers, dendrimers adhere to UCNPs by donating only a fraction of their peripheral groups to the UCNP-surface interactions. The remaining termini make up an interface between the nanoparticle and the aqueous phase, enhancing solubility and offering multiple possibilities for subsequent modification. Using optical probes as dendrimer cores makes it possible to couple the UCNPs signal to analyte-sensitive detection via UCNP-to-chromophore excitation energy transfer (EET). As an example, we demonstrate that UCNPs modified with porphyrin-dendrimers can operate as upconverting ratiometric pH nanosensors. Dendritic UCNPs possess excellent photostability, solubility, and biocompatibility, which make them directly suitable for in vivo imaging. Polyglutamic dendritic UCNPs injected in the blood of a mouse allowed mapping of the cortical vasculature down to 400 μm under the tissue surface, thus demonstrating feasibility of in vivo high-resolution two-photon microscopy with continuous wave (CW) excitation sources. Dendrimerization as a method of solubilization of UCNPs opens up numerous possibilities for use of these unique agents in biological imaging and sensing.

Epigenetic changes involved in cancer development, unlike genetic changes, are reversible. DNA methyltransferase and histone deacetylase inhibitors show antiproliferative effects in vitro, through tumor suppressor reactivation and induction of apoptosis. Such inhibitors have shown activity in the treatment of hematologic disorders but there is little data concerning their effectiveness in treatment of solid tumors. FHIT, WWOX and other tumor suppressor genes are frequently epigenetically inactivated in lung cancers. Lung cancer cell clones carrying conditional FHIT or WWOX transgenes showed significant suppression of xenograft tumor growth after induction of expression of the FHIT or WWOX transgene, suggesting that treatments to restore endogenous Fhit and Wwox expression in lung cancers would result in decreased tumorigenicity. H1299 lung cancer cells, lacking Fhit, Wwox, p16 INK4a and Rassf1a expression due to epigenetic modifications, were used to assess efficacy of epigenetically targeted protocols in suppressing growth of lung tumors, by injection of 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299 tumors. High doses of intraperitoneal AZA/TSA suppressed growth of small tumors but did not affect large tumors (200 mm 3 ); lower AZA doses, administered intraperitoneally or intratumorally, suppressed growth of small tumors without apparent toxicity. Responding tumors showed restoration of Fhit, Wwox, p16 INKa , Rassf1a expression, low mitotic activity, high apoptotic fraction and activation of caspase 3. These preclinical studies show the therapeutic potential of restoration of tumor suppressor expression through epigenetic modulation and the promise of re-expressed tumor suppressors as markers and effectors of the responses. ' 2006 Wiley-Liss, Inc.Key words: DNA methylation; tumor suppressor genes; 5-aza-2-deoxycytidine Lung cancer is the leading cause of cancer death in the western hemisphere for men and women, eclipsing the combined mortalities from breast, colon and prostate cancers. Genomic aberrations involving chromosome 3p are the most frequent and earliest genetic events in lung carcinogenesis. 1,2 In particular, the FHIT gene, spanning the human common fragile site, FRA3B, at chromosome 3p14.2, and the RASSF1A gene at 3p21 are frequently silenced in lung cancer and show hallmarks of tumor suppressor genes. 3 FHIT is altered in many other types of cancers, including breast, head and neck, cervical, bladder, esophageal, gastric, pancreatic and renal cancer and alterations occur in very early stages of preneoplasia in some organs. Fhit loss is associated with progression and outcome in cancers of various organs. 4 Similarly, the WWOX gene at FRA16D is frequently silenced in lung cancers, and has recently been shown to suppress growth of lung cancer cells in nude mice. [5][6][7] The RASSF1A promoter region is hypermethylated in a large fraction of lung and other cancers 8,9 and methylation of the RASSF1A regulatory region has been proposed as a biomarker of lung ca...

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Introduction: In this communication we report on a novel non-invasive methodology in utilizing "soft" energy diagnostic X-rays to indirectly activate a photo-agent utilized in photodynamic therapy (PDT): Photofrin II (Photo II) through X-ray induced luminescence from Gadolinium Oxysulfide (20 micron dimension) particles doped with Terbium: Gd2O2S:Tb. Photodynamic agents such as Photo II utilized in PDT possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through (visible light) photon absorption, the agents exert their cellular cytotoxicity through type I and type II pathways through extensive generation of reactive oxygen species (ROS); namely, singlet oxygen 1 O2, superoxide anion O − 2 , and hydrogen peroxide H2O2, within the intra-tumoral environment. Unfortunately, due to shallow visible light penetration depth (∼ 2 mm to 5 mm) in tissues, the current PDT strategy has largely been restricted to the treatment of surface tumors, such as the melanomas. Additional invasive strategies through optical fibers are currently utilized in getting the visible light into the intended deep seated targets within the body for PDT.Methods: X-ray induced visible luminescence from Gd2O2S:Tb particles were spectroscopically characterized, and the potential in-vitro cellular cytotoxicity of Gd2O2S:Tb particles on human glioblastoma cells (due to 48 Hrs Gd2O2S:Tb particle exposure) was screened through the MTS cellular metabolic assay. In-vitro human glioblastoma cellular exposures in presence of Photo II with Gd2O2S:Tb particles were performed in the dark in sterile 96 well tissue culture plates, and the corresponding changes in the metabolic activities of the glioblastoma due to 15 minutes of (diagnostic energy) X-ray exposure was determined 48 Hrs after treatment through the MTS assay.Results: Severe suppression (> 90% relative to controls) in the cellular metabolic activity of human glioblastoma was measured due to the treatment of clinically relevant concentrations of 20 µg/ml Photo II, with Gd2O2S:Tb particles, and (120 kVp) diagnostic X-rays. Taken together, the in-vitro findings herein provide the basis for future studies in determining the safety and efficacy of this non-invasive X-ray induced luminescence strategy in activating photo-agent in deep seated tumors.

UCNP/Janus-dendrimers enable high-resolution two-photon imaging in the brain up to 1 mm-deep under low-power CW excitation. However, ratiometric sensing using UCNPs and excitation energy transfer is strongly obstructed by tissue absorption.

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