Graphical abstract Highlights • Hep-2 xenograft tumor model and the SLN in rabbits after administration of the PEGylated Au DENPs could be efficient imaged. • The formed PEG-Au DENPs were non-cytotoxic in the given concentration range. • The PEG-Au DENPs could be uptaken predominantly in the lyososomes of the cells. Abstract We report the utilization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for enhanced computed tomography (CT) imaging of human laryngeal squamous carcinoma and indirect CT lymphography imaging in New Zealand rabbits. In this work, PEG-modified amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH 2 ) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The formed PEGylated Au DENPs was used for both enhanced CT imaging of human laryngeal squamous carcinoma cells (Hep-2 cells) and the xenograft tumor mode, and indirect CT lymphography imaging in New Zealand rabbits. In vitro cytotoxicity assay, flow cytometry analysis, and cell morphology observation revealed that the formed PEGylated Au DENPs were non-cytotoxic at a Au concentration up to 400 μM for 24 h and indicated their good biocompatibility. Transmission electron microscopy data confirmed that the PEGylated Au DENPs was uptaken dominantly by the lysosomes of the cells. The PEGylated Au DENPs enabled not only enhance CT imaging of a xenograft tumor model in nude mice after intravenous injection of the particles, but also effective indirect CT lymphography imaging in rabbits. These findings suggest that the designed PEGylated Au DENPs can be used as a potentially effective contrast agent for CT imaging of various biological systems and different kinds of carcinoma, especially lymphatic mapping and human laryngeal squamous carcinoma.

Abstract We demonstrate both theoretically and experimentally that the power density of resonant tunneling diode (RTD) can be enhanced by optimizing emitter spacer layer thickness, in addition to reducing barrier thickness. Compared to the widely used epitaxial structure with ultrathin emitter spacer layer thickness, appropriate increasing the thickness will increase the voltage drop in accumulation region, leading to larger voltage widths of negative differential resistance region. By measuring J-V characteristics, the specific contact resistivity, and the self-capacitance, we theoretically analyze the maximum output power of the fabricated RTDs. It shows that the optimized In 0.8 Ga 0.2 As/AlAs RTD with 20 nm emitter spacer thickness and 5 μm 2 mesa area theoretically possesses the capability to reach 3.1 mW at 300 GHz and 1.8 mW at 600 GHz. Highlights • The power density of resonant tunneling diode can be enhanced by optimizing emitter spacer layer thickness. • The optimized In 0.8 Ga 0.2 As/AlAs RTD possesses the capability to reach 3.1 mW at 300 GHz and 1.8 mW at 600 GHz. • The improved fabrication process based on the previous work can precisely control the mesa area of RTDs. • Optimizing ESL thickness provides an efficient way to balance the cut-off frequency and output power of THz RTD oscillators.

A recently invented duodenal-jejunal bypass sleeve (DJBS) implanted in the duodenum and proximal jejunum has exhibited good glycemic control in diabetes mellitus. However, the specific mechanism by which DJBS placement induces the remission of diabetes is not well known. Previous studies have indicated that changes in the pattern of gut hormone secretion may play a role. The aim of the present study was to explore the role of intestinal L cells and the production of glucagon-like peptide-1 (GLP-1) by these cells in DJBS implantation-induced glycemic control in diabetic rats. A DJBS was placed in the proximal small intestine of rats with diabetes induced by a high-fat diet and low-dose streptozotocin (STZ), and the effects of the DJBS on the remission of diabetes and the GLP-1 levels of plasma and intestinal tissues were investigated 12 weeks after DJBS placement. The number of intestinal GLP-1 positive cells was also counted. When the DJBS had been in place for 12 weeks, the plasma glucose level of the DJBS-implanted rats decreased significantly from 23.33±1.56 mmol/l prior to surgery to 7.70±0.84 mmol/l and the diabetes mellitus was relieved completely; however, diabetic control rats and diabetic rats subjected to sham surgery did not show any improvement. Parallel with the remission of diabetes, the plasma and distal ileum GLP-1 levels of rats in the DJBS implantation group were also higher than those of rats in the diabetic control and sham surgery groups. The number of GLP-1-positive cells in the distal ileum was also higher in the DJBS implantation group than in the diabetic control and sham surgery groups (31.0±2.6 vs. 23.5±4.4 vs. 23.0±3.2 respectively; P<0.01). DJBS implantation effectively led to the remission of diabetes in rats with diabetes induced by a high-fat diet and low-dose STZ when implanted for 12 weeks. The remission of diabetes may be associated with the increase in the number of L cells and elevation of GLP-1 levels induced by DJBS implantation.

All kinds of compound bio-electrets of I&III collagen/chitosan have been developed. Their TSDC curves are analyzed, and the compound bio-electret I&III collagen/chitosan whose T/spl alpha/ and I/spl alpha/ is 37/spl deg/C and 2/spl times/10/sup -9/ A respectively in the polarized state is selected. The study shows that the compound bio-electret can promote normal cell growth when single negatively polarized, and can inhibit cancer cell growth when single positively polarized. It proves that the rational designation of compound bio-electret has a broad applicable use to clinical medicine.

In relation to the natural electret properties and biological function of collagen, we have studied the bioelectret properties of several kinds of collagen electret membrane, which include I&III collagen, II collagen, the compound membrane of I&III collagen and II collagen and placenta collagen, using a TSDC instrument. We discovered that the defect of a disproportionally high T/sub /spl alpha// can be surmounted after polarizing and improving the method of forming the membrane. Rational complexing of different types of collagen can improve the materials' electret properties to meet clinical medical use.

Non-invasive diagnosis and detection of early-stage tumors is regarded as one of the current challenges in the biomedical sciences. Magnetic resonance (MR) imaging is a powerful； non-invasive imaging technique because of its high spatial resolution and tomographic capabilities. However； the signal sensitivity of MR imaging for specific biological targets is largely dependent on the specificity and selectivity of the ligand used to target magnetic nanoparticles (NPs) to specific tissues. Development of tumor-targeted magnetic NPs is necessary to enhance the MR signal sensitivity for in-vivo tumor detection. Various proteins such as transferrin； anti-carcinoembryonic antigen monoclonal antibody rch 24； herceptin； and chlorotoxin have been conjugated onto iron oxide NP surfaces. Unfortunately； these protein ligands tend to display immunogenecity and the biological macromolecules used are very expensive and not available for many types of cancer； which thereby limits their applications. One of the most widely used cancer-targeting ligands is folic acid (FA)； which targets FA receptors (FAR) that are overexpressed in several human carcinomas including breast； ovary； endometrium； kidney； lung； head and neck； brain； and myeloid cancers. Several groups have investigated the conjugation of folic acid (FA) onto iron oxide NPs for targeting tumor cells. However； many of these reports are limited to in-vitro studies. This is largely a result of difficulties related to the in-vivo stability and

The soybean GH3 gene is transcriptionally induced in a wide variety of tissues and organs within minutes after auxin application. To determine the sequence elements that confer auxin inducibility to the GH3 promoter, we used gel mobility shift assays, methylation interference, deletion analysis, linker scanning, site-directed mutagenesis, and gain-of-function analysis with a minimal cauliflower mosaic virus 35s promoter. We identified at least three sequence elements within the GH3 promoter that are auxin inducible and can function independently of one another. Two of these elements are found in a 76-bp fragment, and these consist of two independent 25and 32-bp auxin-inducible elements. Both of these 25and 32-bp auxin-inducible elements contain the sequence TGTCTC just upstream of an AATAAG. An additional auxininducible element was found upstream of the 76-bp auxin-inducible fragment； this can function independently of the 76-bp fragment. Two TGA-box or Hex-like elements (TGACGTAA and TGACGTGGC) in the promoter, which are strong binding sites for proteins in plant nuclear extracts, may also elevate the level of auxin inducibility of the GH3 promoter. The multiple auxin-inducible elements within the GH3 promoter contribute incrementally to the overall level of auxin induction observed with this promoter.

Air pollution is associated with the increased risk of metabolic syndrome. In this study, we performed inhalation exposure of mice fed normal chow or a high-fat diet to airborne fine particulate matters (PM2.5), and then investigated the complex effects and mechanisms of inhalation exposure to PM2.5 on hepatic steatosis, a precursor or manifestation of metabolic syndrome. Our studies demonstrated that inhalation exposure of mice fed normal chow to concentrated ambient PM2.5 repressed hepatic transcriptional regulators involved in fatty acid oxidation and lipolysis, and thus promoted hepatic steatosis. However, PM2.5 exposure relieved hepatic steatosis in high-fat diet-induced obese mice. Further investigation revealed that inhalation exposure to PM2.5 induced hepatic autophagy in mouse livers in a manner depending on the MyD88-mediated inflammatory pathway. The counteractive effect of PM2.5 exposure on high-fat diet-induced hepatic steatosis was mediated through PM2.5-induced hepatic autophagy. The findings from this study not only defined the effects and mechanisms of PM2.5 exposure in metabolic disorders, but also revealed the pleotrophic acts of an environmental stressor in a complex stress system relevant to public health.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.

In this study； we synthesized dendrimer-functionalized laponite (LAP) nanodisks for loading and delivery of anticancer drug doxorubicin (DOX). Firstly； LAP was modified with silane coupling agents and succinic anhydride to render abundant carboxyl groups on the surface of LAP. Then； poly(amidoamine) (PAMAM) dendrimer of generation 2 (G2) were conjugated to form LM-G2 nanodisks. Anticancer drug DOX was then loaded on the LM-G2 with an impressively high drug loading efficiency of 98.4% and could be released in a pH-sensitive and sustained manner. Moreover； cell viability assay results indicate that LM-G2/DOX complexes could more effectively inhibit the proliferation of KB cells (a human epithelial carcinoma cell line) than free DOX at the same drug concentration. Flow cytometry analysis and confocal laser scanning microscope demonstrated that LM-G2/DOX could be uptaken by KB cells more effectively than free DOX. Considering the exceptional high drug loading efficiency and the abundant dendrimer amine groups on the surface that can be further modified； the developed LM-G2 nanodisks may hold a great promise to be used as a novel platform for anticancer drug delivery.

Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups； multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

The fabrication of cobalt oxide nanotubes (length 3-4 μm； width 200-400 nm) was achieved by a colloidal templating approach. In this approach； a Co(III)-cysteinato complex [Co(en)2(S-cys)]2(BF4) was employed as the precursor of cobalt oxide. The infiltration behavior of the precursor into polyelectrolyte multilayers was studied with a quartz crystal microbalance which showed that the amount of the precursor incorporated increased with the number of polyelectrolyte (PE) layers. After incorporation of the precursor into PE multilayers precoated onto submicron-sized polystyrene latex particles via the layer-by-layer deposition； the resulting composite colloidal particles became threaded in a pearl necklace-like structure. Upon calcination at an elevated temperature； cobalt oxide nanotubes were observed by transmission electronic microscopy (TEM) and atomic force microscopy. High-resolution TEM； electron diffraction； energy-dispersive X-ray spectroscopy； and X-ray diffraction showed that these nanotubes were composed of spinel polycrystalline Co3O4. The preparation of such cobalt oxide nanotubes affords a new avenue for the application of metal complexes and represents a promising route for the synthesis of novel inorganic nanotubes.

Several water-soluble cobalt(III) complexes were employed as precursors to form cobalt oxide nanostructures. These complexes were incorporated into polyelectrolyte multilayers precoated onto colloidal particles, followed by calcination. Cobalt complexes with strong intermolecular hydrogen bonding form one-dimensional Co3O4 nanotube structures. Short Co3O4 nanotubes with defects and broken spheres are formed when cobalt complexes with weak or no intermolecular hydrogen bonding are used. The sites for disulfide bond formation present on some complexes were found to be unessential for the nanotube formation. A great deal of effort has been directed toward the synthesis of one-dimensional (1-D) nanostructured materials with a high aspect ratio (e.g., nanotubes).1,2 The unique properties of these materials could find application in areas as diverse as electronics, optics, materials research, and medical science.1-4 Numerous papers have been published on the preparation and characterization of these new materials.5-16 These materials include, but are not limited to, carbon nanotubes,5-8 WS2, MoS2, BN,11 V2O5, TiO2, Al2O3, SiO2, and the recently reported bismuth nanotubes.16 Despite the tremendous amount of work on the development of synthetic methodologies for and the exploration of various applications of these materials, there has been limited work about the elucidation of the relationship between the chemical nature of the materials involved in the syntheses and the final nanostructures. Nevertheless, several recent papers addressing this issue15,17-19 indicate that it is important to understand the mechanism for the formation of these 1-D structures if optimizing the preparative procedures and tailoring the functionality of the final materials are desired. We wish to report the effect of altering the functional groups of the precursors incorporated into polyelectrolyte (PE) multilayers predeposited onto colloidal particles on the final shapes of the nanomaterials. Recently, the treatment of precursors incorporated into the PE multilayers coated onto templates, such as nanosphere,20 nanorod,21 and planar surface,22 has been demonstrated by Caruso and co-workers to be a versatile technique for the synthesis of nanomaterials. Thus far, it appears that shapes of the as-prepared materials are generally dictated by those of the templates. We show here that fine-tuning the chemical structures of the precursors incorporated into the PE multilayers can have a profound influence on the shapes of the resultant nanomaterials. In our approach, polystyrene (PS) colloidal particles (640 nm in diameter, measured by AFM) were precoated with PE multilayers via the layer-by-layer (LbL) method, followed by infiltration of a precursor (e.g., precursor 1, (cysteinatoN,S)bis(ethylenediamine)cobalt(III), shown in Figure 1).23 Broken hollow cobalt oxide nanospheres were initially expected from calcination of the template because the PE/ precursor-coated colloidal templates are spherical (Route 1 in Figure 2).20 Surprisingly, exclusive formation of cobalt oxide nanotubes was observed. We found that the use of precursor 1 caused these colloidal particles to aggregate into a unique pearl necklace-like structure that we believe is the new template for the nanotube formation.24 This new procedure should complement other existing methods for the production of inorganic nanotubes.9-16 Thus, the chemical origin for threading the PE/precursor-coated PS nanospheres * To whom correspondence should be addressed. Dr. F. Zhou: E-mail: fzhou@calstatela.edu； Phone: (323)343-2390； Fax: (323)343-6490. Dr. M. Selke: E-mail: mselke@calstatela.edu. NANO LETTERS 2002 Vol. 2, No. 4 289-293 10.1021/nl0156944 CCC: $22.00 © 2002 American Chemical Society Published on Web 02/21/2002 (Route 2 in Figure 2) merits a detailed investigation. Precursor 1 is capable of forming both intermolecular hydrogen bonding (through the free acid group) and disulfide bonds (through the oxidation of the thiolato group). Because an attempt of using FTIR to detect any peaks associated with the S-S stretching of the putative disulfide bond was not successful (presumably due to the overwhelming background signals arising from the abundant PE and PS molecules), we decided to investigate the mechanism by varying the functional groups on the precursor to prohibit either the intermolecular H-bonding or disulfide bond formation. In addition to precursor 1, three other cobalt complexes (structures shown in Figure 1) were employed as precursors.25 In designing these precursors, several criteria were followed in order to keep the preparative parameters for the nanomaterials constant. First, all of these precursors are water soluble and contain a Co(III) center coordinated by ethylenediamine ligands. Second, the cations bear the same number of charges (2；). Finally, the functional groups on all the precursors have been systematically varied. Specifically, the sulfenato complex (precursor 2) can only form hydrogen bonding (disulfide bond formation is not possible because the thiolato group has been oxidized) and the coordinated water molecule in precursor 3 should form much weaker hydrogen bonds both for steric and electronic reasons. Precursor 4 cannot form H-bonds but might form a disulfide bond through linking unoxidized sulfide sites on two adjacent molecules. We first employed a flow-injection quartz crystal microbalance (FI-QCM)26 to study the infiltration behavior of the four precursors at crystals precoated with PE multilayers. The FI-QCM can monitor the incorporation of the precursors into the PE layers in situ and provide insight to the relationship between the precursor structure and the amount of precursor infiltration. Figure 3a shows the time-resolved QCM response to the precursor infiltration. It is clear that the amount of infiltration increased with the PE layer number. The linear dependence of the amount of precursor incorporated on the number of PE layers is shown in the inset (R2 value ) 0.995). As can be seen, the incorporation of a greater quantity of a given precursor into a thicker PE film suggests that the extent of precursor infiltration can be precisely controlled by varying the number of PE layers. When the outermost PE layer was changed to the positively charged PDADMAC, no precursor incorporation was observed. As shown in recent work by Caruso and co-workers,22 the incorporation of a precursor into the PE layers should be driven by the electrostatic attraction between the positively charged precursor and the negatively charges on the outermost PE layer (i.e., the negatively charged PSS). We also compared the difference in the infiltration behavior among the different precursors. Figure 3b displays a series of FIQCM responses showing the amounts of precursors infiltrated at films of the same number of PE layers. The fact that all precursors can be incorporated into the PE layers suggests that they are suitable candidates for the formation of either type of nanomaterials shown in Figure 2. The analogous QCM responses between precursors 1 and 2 could be ascribed to the similarities in their molecular weights and structures. The other two precursors exhibited different QCM responses with either a smaller (precursor 3) or a larger (precursor 4) mass change than that associated with precursors 1 and 2. The different QCM responses shown by the four precursors appear to be reflective of the difference among their chemical structures. The colloidal particles incorporating different precursors were found to aggregate differently in solutions. Figure 4a is a representative TEM image showing the pearl necklacelike structure that interconnects colloidal particles containing PE/precursor 2, which is analogous to that derived from precursor 1.24 However, the PS nanospheres incorporating precursor 3 or 4 were found to produce only randomly dispersed particles (Figure 4b). It is interesting to note that PS particles with PE coatings loaded with precursor 1 and 2 Figure 1. Structures of the four cobalt (III) complexes used as precursors. Figure 2. Schematic representation of the two possible routes for the formation of cobalt oxide nanostructures. 290 Nano Lett., Vol. 2, No. 4, 2002 did not yield 2or 3-D structures. Although the exact reason for the preferential formation of the 1-D structure is not entirely clear, we believe that it is possible that adjoining two colloidal particles requires a relatively large number of H-bonds and the pearl necklace-like structure facilitates the formation of a greater number of intermolecular H-bonds between two adjacent colloidal particles. Because only one free acid group (the essential moiety for H-bond formation) is present on each octahedral Co(III) in precursor 1 or 2, the number of H-bonds between most colloidal particles would be reduced by the congested particle arrangement associated with the 2or 3-D structure. Consequently, formation of the 1-D structure comprising interconnected particles is more stable than that of the 2or 3-D structure. We finally examined the shapes of the cobalt-containing nanomaterials calcined from precursors infiltrated into 5 bilayers of PDADMAC/PSS pre-deposited onto PS particles. Figure 5 shows a SEM image of a cobalt oxide nanotube produced from calcination of the PS particles coated with PE layers containing precursor 1 or 2. To further confirm the formation of cobalt oxide nanostructures, AFM and TEM measurements were carried out. Figure 6 displays AFM and TEM micrographs of the cobalt oxide nanostructures.27 Bundles of cobalt oxide nanotubes were also observed by AFM.24 AFM images indicated that both precursors 1 and 2 yielded long nanotubes (Figure 6a and 6c). The tubular characteristics were further confirmed by the TEM image (Figure 6b). The length and diameter of the nanotubes were 3-4 μm and 200-400 nm, respectively. X-ray diffraction27 and selected area electron diffraction (SAED) patterns of nanotubes derived from both precursors all indicate that their compositions are of polycrystalline spinel Co3O4. Energydispersive X-ray spectroscopy showed only signals associated with cobalt upon calcination,24 suggesting that all of the organic components from the precursor, the PE layers, and the PS cores had been removed. When precursor 3 was used, the resultant nanomaterials were found to be either shorter tubes and/or broken spheres with many defects (Figure 6d Figure 3. Time-resolved QCM responses to the injections of (a) 250 μL of a 64 mM precursor 1 solution into a flow cell housing a Au-coated quartz crystal precoated with different numbers of PDADMAC/PSS bilayers and (b) 250 μL of the different precursor solutions (All had a concentration of 64 mM) into a flow cell housing crystals coated with 10 PE layers. Arrows indicate the time (200 s) when injections were made. The inset of Figure 3a is a plot of mass change versus the PE layer number. Figure 4. TEM images showing the pearl necklace-like structure containing PE layers loaded with precursor 2 (a) and the random colloidal particles containing PE layers loaded with precursor 4 (b). The PS particles (diameter 640 nm) were precoated with 5 bilayers of PDADMAC/PSS. Figure 5. SEM image of a cobalt oxide nanotube produced from calcination of PS particles coated with PE layers containing precursor 1 or 2. Nano Lett., Vol. 2, No. 4, 2002 291 and 6e), whereas precursor 4 resulted in products that consisted of predominantly broken nanospheres. SAED and XRD analyses demonstrated that the formed nanostructures were also composed of spinel Co3O4 with polycrystaline phases. As suggested above, the formation of Co3O4 nanotubes should originate from calcination of the pearl necklace-like structure. The PE shells separating the interconnected colloidal particles might have been ruptured by the gaseous species from the calcination step. Portions of the PE shells that were not between the colloidal particles experienced a smaller gas pressure and remained intact. With the increased calcination time, these shells further sinter and evolved into rigid nanotube structures of Co3O4. These processes are pictorially shown by Route 2 in Figure 2. It appears that the prerequisite for the nanotube formation is the interconnection of several precursor/PE-coated nanospheres to form a new template, and the sole driving force for such an interconnection is the intermolecular H-bonding formation. This conclusion is supported by the observation that weaker H-bonding (precursor 3) or no H-bonding (precursor 4) can only give rise to much shorter nanotubes or broken nanospheres. In any case, it is apparent that disulfide bond formation (if any) is not an important factor for creating the nanotubes. Our conclusions are in agreement with several recent reports on the effect of H-bonding for the formation of linear tubular structures derived from cyclic polypeptides,17 for the synthesis of nanotubes originated from organic calix[4]hydroquinone,18 and for the production of tubular silica structures from organogel templates.19 In summary, the mechanism for the formation of cobalt oxide nanotubes fabricated via a new route involving calcination of cobalt complex precursor/PE layers coated onto colloidal particles has been elucidated. This is accomplished by systematically varying the functional groups on the cobalt complex precursors. Although all precursors result in the formation of polycrystalline Co3O4, the shapes of the final products were found to be highly dependent on the functional groups on the precursors. When intermolecular H-bonding formation is favored, an interesting pearl necklace-like Figure 6. AFM images of cobalt oxide nanostructures derived from the calcination of the various precursors incorporated into the PE layers precoated onto the PS particles. Images (a), (c), (d), and (f) represent the nanostructures from precursors 1, 2, 3, and 4, respectively. The TEM images in (b) and (e) show cobalt oxide nanostructures produced from calcination of precursors 1 and 3 incorporated into the PE coatings on the PS particles, respectively. 292 Nano Lett., Vol. 2, No. 4, 2002 structure composed of several precursor/PE-coated colloidal particles can be formed in the solution and serves as the new template for the eventual nanotube formation. Our results demonstrate that shapes of nanomaterials produced through this scheme are related not only to the preparative parameters, but also to the presence of specific functional groups on the precursor molecules. Acknowledgment. We thank Julia Pilloni and Jiaxing Huang (University of California, Los Angeles) for their assistance with the TEM and SEM measurements and William Wimberley (CSULA) for his help with the TEM image processing. Financial supports from the NIH-SCORE subprojects (GM 08101) and the NSF-CRUI Grant No. (DBI9978806 for F.Z.) is gratefully acknowledged.

Generation 5 ethylenediamine (EDA)-cored poly(amidoamine) (PAMAM) dendrimers (E5, E denotes the EDA core and 5 the generation number) with different degrees of acetylation and carboxylation were synthesized and used as a model system to investigate the effect of charge and the influence of dendrimer surface modifications on electrophoretic mobility (EM) and molecular distribution. The surface-modified dendrimers were characterized by size-exclusion chromatography, 1H NMR, MALDI-TOF-MS, PAGE, and CE. The focus of our study was to determine how EM changes as a function of particle charge and molecular mass, and how the molecular distribution changes due to surface modifications. We demonstrate that partially modified dendrimers have much broader migration peaks than those of fully surface functionalized or unmodified E5 dendrimers due to variations in the substitution of individual dendrimer surfaces. EM decreased nonlinearly with increases in surface acetylation for both PAMAM acetamides and PAMAM succinamic acids, indicating a complex migration activity in CE separations that is not solely due to charge/mass ratio changes. These studies provide new insights into dendrimer properties under an electric field, as well as into the characterization of dendrimer-based materials being developed for medical applications.

Dendrimer-entrapped gold nanoparticles (Au DENPs) can be formed using low-generation dendrimers pre-modified by polyethylene glycol (PEG). The formed PEGylated Au DENPs with desirable stability, cytocompatibility, and X-ray attenuation properties enable efficient computed tomography imaging of the heart and tumor model of mice.

We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays, flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7 (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did not initiate hole formation but expanded holes at existing defects. Acetamide-terminated G5 PAMAM dendrimers did not cause hole formation in this concentration range. The interactions between PAMAM dendrimers and cell membranes were studied in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide-terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However, the dose dependent release of the cytoplasmic proteins lactate dehydrogenase (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5 PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane integrity up to a 500 nM concentration. The induction of permeability caused by the amine-terminated dendrimers was not permanent, and leaking of cytosolic enzymes returned to normal levels upon removal of the dendrimers. The mechanism of how PAMAM dendrimers altered cells was investigated using fluorescence microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1) a hole formation mechanism is consistent with the observations of dendrimer internalization, (2) cytosolic proteins can diffuse out of the cell via these holes, and (3) dye molecules can be detected diffusing into the cell or out of the cell through the same membrane holes. Diffusion of dendrimers through holes is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into cells and is consistent with the lack of uptake of G5 acetamide-terminated PAMAM dendrimers.