The investigation and application of complex nanostructures requires the hierarchical arrangement of distinct domains on a small scale. Herein, we report a method to prepare planet-satellite arrangements using RAFT polymers. Our approach is based on star polymers decorated with trithiocarbonate groups on their outer periphery that attach to gold surfaces and thus provide the polymer with the ability to connect (larger) gold nanoparticle planets with (smaller) gold nanoparticle satellites. By adjusting the molecular weight of the polymeric linker, nanostructures with tailored planet-satellite distances, as evidenced by transmission electron microscopy, are obtained. This strategy offers a straightforward way to prepare gold nanoparticle scaffolds with multiple reactive functionalities at defined distances from the central core.

The ␤-amyloid precursor protein (APP) represents a type I transmembrane glycoprotein that is ubiquitously expressed. In the brain, it is a key player in the molecular pathogenesis of Alzheimer disease. Its physiological function is however less well understood. Previous studies showed that APP is up-regulated in prostate, colon, pancreatic tumor, and oral squamous cell carcinoma. In this study, we show that APP has an essential role in growth control of pancreatic and colon cancer. Abundant APP staining was found in human pancreatic adenocarcinoma and colon cancer tissue. Interestingly, treating pancreatic and colon cancer cells with valproic acid (VPA, 2-propylpentanoic acid), a known histone deacetylase (HDAC) inhibitor, leads to up-regulation of GRP78, an endoplasmic reticulum chaperone immunoglobulin-binding protein. GRP78 is involved in APP maturation and inhibition of tumor cell growth by down-regulation of APP and secreted soluble APP␣. Trichostatin A, a pan-HDAC inhibitor, also lowered APP and increased GRP78 levels. In contrast, treating cells with valpromide, a VPA derivative lacking HDAC inhibitory properties, had no effect on APP levels. VPA did not modify the level of epidermal growth factor receptor, another type I transmembrane protein, and APLP2, a member of the APP family, demonstrating the specificity of the VPA effect on APP. Small interfering RNA-mediated knockdown of APP also resulted in significantly decreased cell growth. Based on these observations, the data suggest that APP downregulation via HDAC inhibition provides a novel mechanism for pancreatic and colon cancer therapy. ␤-Amyloid precursor protein (APP)2 is a highly conserved single transmembrane protein (type I) with a receptor-like structure and consists of a heterogeneous group of proteins migrating between 110 and 135 kDa (1, 2). The heterogeneity is due to alternative splicing, leading to eight distinct isoforms (namely APP677, APP695, APP696, APP714, APP733, APP751, APP752, and APP770), as well as by a variety of post-translational modifications, including O-and N-glycosylation, sulfation, and phosphorylation. APP isoforms exist as immature (N-glycosylated) and mature (N-and O-glycosylated, tyrosylsulfated) species. Immature APP localizes in the endoplasmic reticulum and cis-Golgi, and the mature APP form preferentially localizes in the trans-Golgi network, secretory and endocytic vesicles, and at the plasma membrane (3, 4).APP695 is the most common isoform in the central nervous system, whereas APP751 and APP770 are predominantly expressed in non-neuronal cells (5). The key event in the pathogenic cascade in Alzheimer disease is the amyloidogenic pathway characterized by subsequent cleavage of APP by the enzyme ␤-secretase and further processing by ␥-secretase, which finally leads to the generation of A␤ peptides. However, the predominant route of APP processing consists of successive cleavages by ␣-and ␥-secretases in non-neuronal cells (6, 7). The cleavage of APP at Lys 16 -Leu 17 bond by ␣-secretase within the A␤ sequence ...

A new methodology has been developed for preparing α-functional polymers in a one-pot simultaneous polymerization/isocyanate "click" reaction. Our original synthetic strategy is based on the preparation of a carbonyl-azide chain transfer agent (CTA) precursor that undergoes the Curtius rearrangement in situ during reversible addition-fragmentation chain transfer (RAFT) polymerization yielding well-controlled α-isocyanate modified polymers. This strategy overcomes numerous difficulties associated with the synthesis of a polymerization mediator bearing an isocyanate at the R group and with the handling of such a reactive functionality. This new carbonyl-azide CTA can control the polymerization of a wide range of monomers, including (meth)acrylates, acrylamides, and styrenes (M(n) = 2-30 kDa; Đ = 1.16-1.38). We also show that this carbonyl-azide CTA can be used as a universal platform for the synthesis of α-end-functionalized polymers in a one-pot RAFT polymerization/isocyanate "click" procedure.

Planet-satellite nanostructures from RAFT star polymers and larger (planet) as well as smaller (satellite) gold nanoparticles are analyzed in experiments and computer simulations regarding the influence of arm number of star polymers. A uniform scaling behavior of planet-satellite distances as a function of arm length was found both in the dried state (via transmission electron microscopy) after casting the nanostructures on surfaces and in the colloidally dispersed state (via simulations and small-angle X-ray scattering) when 2-, 3-, and 6-arm star polymers were employed. This indicates that the planet-satellite distances are mainly determined by the arm length of star polymers. The observed discrepancy between TEM and simulated distances can be attributed to the difference of polymer configurations in dried and dispersed state. Our results also show that these distances are controlled by the density of star polymers end groups, and the number of grabbed satellite particles is determined by the magnitude of the corresponding density. These findings demonstrate the feasibility to precisely control the planet-satellite structures at the nanoscale.

A strategy for the controlled assembly of gold nanocrystals into dispersed three-dimensional superstructures is presented. A multifunctional RAFT agent was used to prepare multiblock polystyrene (4.4−17.8 kDa) with trithiocarbonate groups as junctions between the individual blocks. Addition of these polymers to two-phase Brust−Schiffrin gold nanoparticles (4.1 nm) resulted in the formation of stable gold-nanoparticle assemblies dispersed in toluene. TEM analysis revealed that the interparticle distances in these superstructures can be tuned over an unprecedented wide range by employing multiblock polymers with an adjusted degree of polymerization and thus tailored trithiocarbonate distances. Cross-linking of the gold nanoparticles in the assemblies by multifunctional trithiocarbonates was proven by AFM showing partly preserved globular shape after deposition on a solid substrate. The reported strategy is expected to prove useful when interparticle distances in nanoparticle assemblies need to be tuned in a liquid phase or on surfaces. I n recent years, colloidal superparticles 1 attracted growing attention due to potential applications ranging from but not limited to sensing, 2 photothermal therapy, 3 and surfaceenhanced Raman spectroscopy. 4 One of the central requirements for the design and understanding of such particle assemblies is the ability to control the spatial arrangement of the individual particles. 5−7 Due to the chemical stability and facile surface modification of gold nanoparticles (AuNPs), their spherical assemblies in particular are regarded as canonical model superstructures and are explored extensively. 5,7−16 Their formation is driven through cross-linking of individual particles mediated by a variety of distinct interactions, such as salt bridges, 5 hydrogen bonding, 8,9,16 π-π-interactions, 11 metal coordination, 13 dipole− dipole-interactions, 14 halogen bonding, 15 and thiol−gold 12 and thioether−gold interactions. 7,10 The cross-linking species can take the form of dendrimers, 5 small molecules, 7,10−15 DNA, 8 polypeptides, 16 and synthetic polymers. 9 Because small molecules as cross-linking agents suffer from their inherent limitations, 17 polymers are attractive candidates for fulfilling the dual function of (1) providing good particle/assembly dispersion through steric stabilization and (2) directing selfassembly. Moreover, because there are tools available to control complex macromolecular architectures (like reversible-deactivation radical polymerization (RDRP) techniques), it can be envisaged to translate the macromolecular design to the structure of nanoparticle assemblies. 18 Of all RDRP techniques, RAFT polymerization 19 is an attractive means of polymer fabrication in the context of gold nanoparticle chemistry, because RAFT polymers inherently contain the thiocarbonylthio moiety, which can be used as an anchoring group for the attachment to gold surfaces. 20 Our lab recently examined in detail a strategy to prepare multiblock (co)polymers with trithiocarbonate (TTC) groups in...