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Now showing items 33 - 43 of 43

  • Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat Diet by Stimulating Hepatic Autophagy

    Yining Qiu   Ze Zheng   Hyunbae Kim   Zhao Yang   Gary Zhang   Xiangyang Shi   Fei Sun   Changya Peng   Yuchuan Ding   Aixia Wang   Lung-Chi Chen   Sanjay Rajagopalan   Qinghua Sun   Kezhong Zhang  

    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.
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  • Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma

    Ruizhi Wang   Yu Luo   Shuohui Yang   Jiang Lin   Dongmei Gao   Yan Zhao   Jinguo Liu   Xiangyang Shi   Xiaolin Wang  

    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.
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  • Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

    Kangan Li   Shihui Wen   Andrew C. Larson   Mingwu Shen   Zhuoli Zhang   Qian Chen   Xiangyang Shi   Gui-xiang Zhang  

    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.
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  • Formation of Cobalt Oxide Nanotubes: Effect of Intermolecular Hydrogen Bonding between Co(III) Complex Precursors Incorporated onto Colloidal Templates

    Xiangyang Shi   Shubo Han   Raymond J. G. Sanedrin   César P Gálvez   David G. Ho   Billy Hernandez   Feimeng Zhou   Matthias Selke  

    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.
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  • Electrophoretic mobility and molecular distribution studies of poly(amidoamine) dendrimers of defined charges.

    Xiangyang Shi   István Bányai   Keyla Rodriguez   Mohammad Tajul Islam   Wojciech Lesniak   Peter Balogh   Lajos P. Balogh   James R Baker  

    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.
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  • Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma

    Ruizhi Wang   Yu Luo   Shuohui Yang   Julie Qiaojin Lin   Dongmei Gao   Yan Zhao   Jinguo Liu   Xiangyang Shi   Xiaolin Wang  

    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 {(Au)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au)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; {(Au)100G5.NH2-FIDOTA(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.
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  • Synthesis of PEGylated low generation dendrimer-entrapped gold nanoparticles for CT imaging applications.

    Hui Liu   Han Wang   Yanhong Xu   Mingwu Shen   Jinglong Zhao   Gui-xiang Zhang   Xiangyang Shi  

    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.
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  • Multifunctional Fe3O4 @ Au core/shell nanostars: a unique platform for multimode imaging and photothermal therapy of tumors

    Yong Hu   Ruizhi Wang   Shige Wang   Ling Ding   Jingchao Li   Yu Luo   Xiaolin Wang   Mingwu Shen   Xiangyang Shi  

    We herein report the development of multifunctional folic acid (FA)-targeted Fe3O4 @ Au nanostars (NSs) for targeted multi-mode magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. In this present work; citric acid-stabilized Fe3O4/Ag composite nanoparticles prepared by a mild reduction route were utilized as seeds and exposed to the Au growth solution to induce the formation of Fe3O4 @ Au core/shell NSs. Followed by successive decoration of thiolated polyethyleneimine (PEI-SH); FA via a polyethylene glycol spacer; and acetylation of the residual PEI amines; multifunctional Fe3O4 @ Au NSs were formed. The designed multifunctional NSs possess excellent colloidal stability; good cytocompatibility in a given concentration range; and specific recognition to cancer cells overexpressing FA receptors. Due to co-existence of Fe3O4 core and star-shaped Au shell; the NSs can be used for MR and CT imaging of tumors; respectively. Likewise; the near infrared plasmonic absorption feature also enables the NSs to be used for PA imaging and PTT of tumors. Our study clearly demonstrates a unique theranostic nanoplatform that can be used for high performance multi-mode imaging-guided PTT of tumors; which may be extendable for theranostics of different diseases in translational medicine.
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  • Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport.

    Seungpyo Hong   Anna U. Bielinska   Almut Mecke   Balazs Keszler   James L Beals   Xiangyang Shi   Lajos P. Balogh   Bradford G. Orr   James R Baker   Mark M Banaszak Holl  

    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.
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  • Hyaluronic Acid-Modified Magnetic Iron Oxide Nanoparticles for MR Imaging of Surgically Induced Endometriosis Model in Rats

    He Zhang   Jingchao Li   Wenjie Sun   Yong Hu   Guofu Zhang   Mingwu Shen   Xiangyang Shi  

    Endometriosis is defined as the presence of endometrial tissue outside the uterine; which may affect nearly 60% of women in reproductive age. Deep infiltrating endometriosis (DIE) defined as an endometriotic lesion penetrating into the retroperitoneal space or the wall of the pelvic organs to a depth of at least 5 mm represents the most diagnostic challenge. Herein; we reported the use of hyaluronic acid (HA)-modified magnetic iron oxide nanoparticles (HA-Fe3O4 NPs) for magnetic resonance (MR) imaging of endometriotic lesions in the rodent model. Sixteen endometriotic lesions were surgically induced in eight rats by autologous transplantation. Four weeks after lesion induction; three rats were scanned via MR imaging after tail vein injection of the HA-Fe3O4 NPs. Accordingly; the remaining five mice were sacrificed in the corresponding time points. The ectopic uterine tissues (EUTs) were confirmed by histological analysis. Quantification of Fe in the EUT was also performed by inductively coupled plasma-optical emission spectroscopy. Our results showed that by using the HA-Fe3O4 NPs; the EUTs were able to be visualized via T2-weighted MR imaging at 2 hours post injection; corroborating the Prussian blue staining results. The developed HA-Fe3O4 NPs could be used as negative contrast agents for sensitively detecting endometriosis in a mouse model and may be applied for future hyperthermia treatment of endometriosis.
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  • Formation of Uniform Polyaniline Thin Shells and Hollow Capsules Using Polyelectrolyte-Coated Microspheres as Templates

    Xiangyang Shi   Alejandro L. Briseno   Raymond J. G. Sanedrin   Feimeng Zhou  

    Multilayers of poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate) precoated onto melamine formaldehyde (MF) particles via the layer-by-layer (LbL) self-assembly procedure were used as templates for the subsequent deposition of polyaniline (PANI). Transmission electron microscopic (TEM) and scanning electron microscopic (SEM) images reveal that the as-prepared PANIcontaining polyelectrolyte (PE)-MF core-shell particles are narrowly dispersed and possess uniform surface morphology. Intact hollow PANI/PE capsules can also be produced by extracting the MF cores in an acidic solution. FTIR spectra of the hollow capsules indicate that PANI and PE are both present and suggest that the PANI exists in the emeraldine form. The incorporation of PANI in the shells was found to enhance the rigidity of these composite materials; and the PANI/PE-coated MF core-shell particles have comparable conductivities with other PANI-coated colloidal particles. The amount of PANI incorporation was also found to increase with the PE layer number; suggesting that the LbL procedure for forming PE multilayers is a convenient method for modifying the colloidal particle surfaces for a favorable PANI film growth and for controlling the PANI thin shell thickness. The method developed is simple; versatile; and colloidal particle general.
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