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Now showing items 1 - 16 of 49

  • Dendrimer-based contrast agents for PET imaging

    Lingzhou Zhao   Xiangyang Shi   Jinhua Zhao  

    Positron emission tomography (PET) imaging offers physiological and biological information through the in vivo distribution of PET agents for disease diagnosis, therapy monitoring and prognosis evaluation. Due to the unique structural characteristics allowing for facile modification of targeting ligands and radionuclides, dendrimers can be served as a versatile scaffold to build up various PET imaging agents, and significant breakthroughs have been made in this field over the past decades. This review focuses on the recent advances in dendrimer-based contrast agents for PET imaging of cancer, cardiovascular and other diseases. In particular, radiolabeling strategies for different PET isotopes are described in detail. Several challenges involved in clinical translation of radiolabeled dendrimers are also discussed.
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  • Nanogels as Contrast Agents for Molecular Imaging

    Jianzhi Zhu   Wenjie Sun   Xiangyang Shi  

    Nanogels (NGs) as soft nanosized materials have gained a variety of interests in biomedical fields. The versatile NG scaffolds with 3‐dimensional spherical shape, high loading efficiency, tunable surface functionalization, and excellent biocompatibility afford their uses as carrier to load mono‐ or multi‐mode molecular imaging contrast agents (CAs). This review summarizes the synthesis routes and applications of NGs as CAs for molecular imaging applications including magnetic resonance (MR), computed tomography (CT), radionuclide, optical, and dual/multi‐modality imaging.
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  • Dendrimer-based molecular imaging contrast agents

    Zheng Qiao   Xiangyang Shi  

    Abstract This review reports recent advances on the use of dendrimer nanotechnology to build up various contrast agents for different single-mode or dual-mode molecular imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, and tunable surface conjugation chemistry enable the facile modification of dendrimer surface with different imaging agents ( e.g. , fluorescent dyes, traditional small molecular contrast agents, or metal ion/chelator complexes) and targeting ligands, and convenient entrapment, stabilization, and self-assembly to form various organic or organic/inorganic hybrid nanoparticles that can be used as multifunctional contrast agents for both non-radionuclide- and radionuclide-based molecular imaging applications. In particular, strategies used to generate multifunctional nanoprobes for different modes of targeted molecular imaging of cancer are discussed in detail.
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  • Bench-to-bedside translation of dendrimers: Reality or utopia? A concise analysis

    Serge Mignani   João Rodrigues   Helena Tomas   René Roy   Xiangyang Shi   Jean-Pierre Majoral  

    Abstract Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as drug delivery, gene therapy and diagnostic. Up-to-date, very few dendrimers has yet gained regulatory approval for systemic administration, why? In this critical review, we briefly focus on the list of desired basic dendrimer requirements for decision-making purpose by the scientists (go/no-go decision), in early development stages, to become clinical candidates, and to move towards Investigational New Drugs (IND) application submission. In addition, the successful translation between research and clinic should be performed by the implementation of a simple roadmap to jump the ‘valley of death’ successfully. Graphical abstract Image 1
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  • Dendrimer-Functionalized Laponite Nanodisks as a Platform for Anticancer Drug Delivery

    Rania Mustafa   Yu Luo   Yilun Wu   Rui Guo   Xiangyang Shi  

    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.
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  • An RGD-modified hollow silica@Au core/shell nanoplatform for tumor combination therapy

    Xin Li   Lingxi Xing   Yong Hu   Zhijuan Xiong   Ruizhi Wang   Xiaoying Xu   Lianfang Du   Mingwu Shen   Xiangyang Shi  

    Graphical abstract Abstract The combination of chemotherapy and photothermal therapy (PTT) in multifunctional nanoplatforms to improve cancer therapeutic efficacy is of great significance while it still remains to be a challenging task. Herein, we report Au nanostar (NS)-coated hollow mesoporous silica nanocapsules (HMSs) with surface modified by arginine-glycine-aspartic acid (RGD) peptide as a drug delivery system to encapsulate doxorubicin (DOX) for targeted chemotherapy and PTT of tumors. Au NSs-coated HMSs core/shell nanocapsules (HMSs@Au NSs) synthesized previously were conjugated with RGD peptide via a spacer of polyethylene glycol (PEG). We show that the prepared HMSs@Au-PEG-RGD NSs are non-cytotxic in the given concentration range, and have a DOX encapsulation efficiency of 98.6 ± 0.7%. The designed HMSs@Au-PEG-RGD NSs/DOX system can release DOX in a pH/NIR laser dual-responsive manner. Importantly, the formed HMSs@Au-PEG-RGD NSs/DOX nanoplatform can specifically target cancer cells overexpressing α v β 3 intergrin and exert combination chemotherapy and PTT efficacy to the cells in vitro and a xenografted tumor model in vivo . Our results suggest that the designed HMSs@Au-PEG-RGD NSs/DOX nanoplatform may be used for combination chemotherapy and PTT of tumors. Statement of Significance We demonstrate a convenient approach to preparing a novel RGD-targeted drug delivery system of HMSs@Au-PEG-RGD NSs/DOX that possesses pH/NIR laser dual-responsive drug delivery performance for combinational chemotherapy and PTT of tumors. The developed Au NS-coated HMS capsules have both merits of HMS capsules that can be used for high payload drug loading and Au NSs that have NIR laser-induced photothermal conversion efficiency (70.8%) and can be used for PTT of tumors.
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  • Dendrimer-based magnetic iron oxide nanoparticles: their synthesis and biomedical applications

    Wenjie Sun   Serge Mignani   Mingwu Shen   Xiangyang Shi  

    Highlights • Dendrimers with unique properties can used to form multifunctional MIO NPs. • Various synthetic strategies used to form dendrimer-based MIO NPs are summarized. • Dendrimer-based MIO NPs can be used for different biomedical applications. • Outlooks of dendrimer-based MIO NPs for biomedical applications are discussed. Magnetic iron oxide nanoparticles (MIO NPs) bearing different appropriate surface modifications can be prepared using diverse physical and chemical methods. As an ideal macromolecule, dendrimers have attracted considerable attention because of their unique properties, including their three 3D architecture, monodispersity, highly branched macromolecular characteristics, and tunable terminal functionalities. These properties make dendrimers a powerful nanoplatform for the creation of functional organic and/or inorganic hybrid NPs, in particular dendrimer-based MIO NPs. Here, we report on recent advances in the preparation of dendrimer-based MIO NPs for different biomedical applications, such as magnetic resonance (MR) imaging, drug and gene delivery, and protein immobilization. Teaser The development and synthesis of dendrimer-based magnetic iron oxide nanoparticles formed through different synthetic strategies for various biomedical applications are discussed.
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  • Design of electrospun nanofibrous mats for osteogenic differentiation of mesenchymal stem cells

    Shige Wang   Fei Hu   Jingchao Li   Shuping Zhang   Mingwu Shen   Mingxian Huang   Xiangyang Shi  

    Abstract The clinical translation potential of mesenchymal stem cells (MSCs) in regenerative medicine has been greatly exploited. With the merits of high surface area to volume ratio, facile control of components, well retained topography, and the capacity to mimic the native extracellular matrix (ECM), nanofibers have received a great deal of attention as bone tissue engineering scaffolds. Electrospinning has been considered as an efficient approach for scale-up fabrication of nanofibrous materials. Electrospun nanofibers are capable of stimulating cell–matrix interaction to form a cell niche, directing cellular behavior, and promoting the MSCs adhesion and proliferation. In this review, we give a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. Specifically, the influences of biological and physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed. Graphical Abstract This review gives a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. The influences of chemical or physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed. Image 1 Highlights • The application potentials of various kinds of electrospun nanofibers used for MSCs-based bone tissue engineering were summarized. • Inorganic inductive materials with osteoinductive and osteoconductive properties could alter the mechanical property of electrospun nanofibers, which could be then converted to biochemical signals that are able to active the osteogenic differentiation. • Organic cues could be encapsulated by electrospun nanofibers and their release from the nanofiber matrix could be controlled to a sustained release manner so as to realize a better osteogenic differentiation outcome. • Topological cues included fiber diameter, pores, orientation, patterns and other stimuli such as the mechanical property and surface conductivity could direct the cell growth along the aligned nanofiber orientation or micropattern direction to present different cell shapes, which were conductive for specific differentiation of MSCs.
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  • Characterization of crystalline dendrimer-stabilized gold nanoparticles

    Xiangyang Shi   T Rose Ganser   Kai Sun   Lajos P Balogh and James R Baker Jr  

    Monodispersed, highly crystalline dendrimer-stabilized gold nanoparticles (Au DSNPs)were synthesized via hydrazine reduction chemistry and stabilized using primaryamine-terminated poly(amidoamine) (PAMAM) dendrimers of different generations(generations 2–6) with the same molar ratios of dendrimer terminal nitrogen ligands/goldatoms. The sizes of the synthesized Au DSNPs decrease with the increase of the number ofdendrimer generations. These Au DSNPs are fluorescent and display strong blue emissionintensity at 458 nm. Polyacrylamide gel electrophoresis (PAGE) analysis indicates that allAu DSNPs are stable and both metal NPs and dendrimer stabilizers do not separate fromeach other during the electrophoresis process. The synthesized inorganic/organic hybrid AuDSNPs provide new nanoplatforms that will be further modified with variousbiological ligands for the application of biosensing and targeted cancer therapeutics.
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  • Interactions gold/phosphorus dendrimers. Versatile ways to hybrid organic–metallic macromolecules

    Jean Pierre Majoral   Maria Zablocka   Anne-Marie Caminade   Piotr Balczewski   Xiangyang Shi   Serge Mignani  

    Graphical abstract Highlights • Interactions phosphorus dendrimers with Au(I) or Au(III). • Formation of P Au, S Au, P N P  S Au, P N P N P S Au and [N P N] Au bonds. • Nanocrystals of (Au 55 ) x , Au nanoparticles design. • Bioactive multilayer thin films on gold surface. • Anti-tumoral and anti-bacterial properties of gold complexes. Abstract Nanotechnology has the high capability to revolutionize many other technologies in many fields, due to the development of myriad nanodevices. Thus nanoparticles have been extensively studied over the last decade. Among all these, dendrimers pertain to the “nano-world” by virtue of their size (a few nanometers range). However, they are intrinsically different from classical ‘hard’ metallic nanoparticles because they are constituted exclusively of ‘soft’ organic matter (organic polymers). Their nanometric size effects can be observed and are reminiscent to those of the multivalent systems widely known in Nature. In this review we will report ways of incorporation of Au(I) or Au(III) selectively at the level of the core, within the cascade structure, regioselectively at a given generation, or on the outer shell of various phosphorus dendrimers. This can be achieved via the skeleton modification of these phosphorus dendrimers as well as with the selective incorporation of ligands as phosphine, thiol, iminophosphorane, thiophosphine, iminopyridine groups allowing complexation via formation of P Au, S Au, P N P S Au, or N Au N bonds. Original phosphorus dendritic structures as macromolecular asterisks, or onion peel dendritic structures allow to diversify the ways of obtaining either gold complexes or gold nanoparticles, some of them being used as chemical sensors. Finally, selected examples of applications of these gold nano-objects in nanomedicine for neuron activation or unprecedented anti-tumoral properties will be presented.
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  • Capillary electrophoresis of polycationic poly(amidoamine) dendrimers

    Xiangyang Shi   István Bányai   Wojciech G. Lesniak   Mohammad T. Islam   István Országh   Peter Balogh   James R. Baker Jr.   Lajos P. Balogh  

    Generation 2 to generation 5 poly(amidoamine) (PAMAM) dendrimers having different terminal functionalities were analyzed by capillary electrophoresis (CE). Polyacrylamide gel electrophoresis was also used to assess the composition of the individual generations for comparison with the CE results. Separation of PAMAMs can be accomplished by either using uncoated silica or silanized silica capillaries, although reproducibility is poor using the uncoated silica capillary. To improve run-to-run reproducibility, silanized capillary was used and various internal standards were also tested. Relative and normalized migration times of primary amine terminated PAMAM dendrimers were then determined using 2,3-diaminopyridine (2,3-DAP) as an internal standard. Using silanized capillaries and internal standards, the relative and normalized migration times are fully reproducible and comparable between runs. Apparent dimensionless electrophoretic mobilities were determined and the results were compared to theoretical calculations. It is concluded that for PAMAMs a complex separation mechanism has to be considered in CE, where the movement of the ions is due to the electric field, but the separation is rather the consequence of the adsorption/desorption equilibria on the capillary wall ("electrokinetic capillary chromatography"). The described method may be used for quality control and may serve as an effective technique to analyze polycationic PAMAM dendrimers and their derivatives with different surface modifications.
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  • Dendrimer-Entrapped Gold Nanoparticles as a Platform for Cancer-Cell Targeting and Imaging

    Xiangyang Shi   Suhe Wang   Sasha Meshinchi   Mary?E. Van Antwerp   Xiangdong Bi   Inhan Lee   James?R. Baker Jr.  

    We present a general approach for the targeting and imaging of cancer cells using dendrimer-entrapped gold nanoparticles (Au DENPs). Au DENPs were found to be able to covalently link with targeting and imaging ligands for subsequent cancer-cell targeting and imaging. The Au DENPs linked with defined numbers of folic acid (FA) and fluorescein isothiocyanate (FI) molecules are water soluble, stable, and biocompatible. In vitro studies show that the FA- and Fl-modified Au DENPs can specifically bind to KB cells (a human epithelial carcinoma cell line) that overexpress high-affinity folate receptors and they are internalized dominantly into lysosomes of target cells within 2 h. These findings demonstrate that Au DENPs may serve as a general platform for cancer imaging and therapeutics.
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  • Synthesis, characterization, and manipulation of dendrimer-stabilized iron sulfidenanoparticles

    Xiangyang Shi   Kai Sun   Lajos P Balogh and James R Baker Jr  

    FeS nanoparticles (NPs) were synthesized using ethylenediamine corepoly(amidoamine) (PAMAM) dendrimers of generation 4 terminated with amino(G4·NH2), hydroxyl(G4·NGlyOH), andcarboxyl (G4·SAH) groups, respectively, as stabilizers. These dendrimer-stabilized FeS NPs (FeS DSNPs) werecharacterized by ultraviolet–visible (UV–vis) spectrometry, zeta-potential measurements,and transmission electron microscopy (TEM). Deposition of FeS NPs onto mesoporoussilica gel microparticles was attempted using two approaches: (A) direct coating of{FeS–G4·NH2} DSNPs onto silica particles; and (B) usingG4·NH2-coated silica particlesto incorporate Fe2+ ions for the subsequent formation of FeS NPs. Scanning electron microscopy (SEM) studiesshow that approach (B) was much more efficient in the incorporation of FeS NPs thanapproach (A). Such preparation and manipulation of FeS DSNPs provides a uniquestrategy for fabricating various reactive nanoplatforms for environmental remediationapplications.
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  • Loading of Au/Ag bimetallic nanoparticles within electrospun PVA/PEI nanofibers for catalytic applications

    Dengmai Hu   Yunchao Xiao   Hui Liu   Hong Wang   Jingchao Li   Benqing Zhou   Pengchao Liu   Mingwu Shen   Xiangyang Shi  

    Graphical abstract Abstract We present a convenient method to immobilize Au/Ag nanoparticles (NPs) within electrospun polyvinyl alcohol (PVA)/polyethylenimine (PEI) nanofibers by in-situ reduction for catalytic applications. Water-stable electrospun PVA/PEI nanofibers were initially fabricated by crosslinking with glutaraldehyde (GA) vapor. Then, the nanofibers were used as a nanoreactor to bind Au salt via electrostatic interaction with the free PEI amines, followed by NaBH 4 reduction to form Au NPs. The formed Au NP-containing nanofibers were then used to bind Ag + ions via chelation with the free PEI amines, followed by reduction with ascorbic acid to form the Au/Ag NP-loaded PVA/PEI nanofibers. The small size (4.9 ± 1.8 nm) and narrow size distribution of the immobilized Au/Ag NPs reveal that the nanofibrous structure is able to efficiently prevent the aggregation of the NPs. We then evaluated the catalytic activity and reusability of Au/Ag NP-immobilized PVA/PEI nanofiers by catalytic transformation of 4-nitrophenol to 4-aminophenol in aqueous solution. The material exhibited excellent catalytic efficiency and reusability. The developed approach could be applied to create other bimetallic NP-incorporated nanofibers for catalysis, tissue engineering, and environmental remediation applications.
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  • Generational, skeletal and substitutional diversities in generation one poly(amidoamine) dendrimers

    Xiangyang Shi   István Bányai   Mohammad T. Islam   Wojciech Lesniak   Denzel Z. Davis   James R. Baker Jr   Lajos P. Balogh  

    Structural deviations of ethylenediamine core polyamidoamine (PAMAM) dendrimers and derivatives can be defined as skeletal and/or substitutional diversities. Detailed analysis of dendrimer starting materials and derivatives is necessary to understand the intrinsic characteristics of commercial dendrimer materials and their variations related to subsequent surface modifications. In this paper, structural deviations of ethylenediamine core generation 1 PAMAM dendrimers (PAMAM_E1 or E1) are studied and determined in a frame of a systematic investigation using combined characterization techniques. A primary amine-terminated PAMAM dendrimer of generation 1 (E1.NH 2) was used as a starting material to synthesize glycidol (E1.N(Gly)OH) and acetamide-terminated (E1.NHAc) dendrimers. The purity and homogeneity of these dendrimers were extensively characterized by polyacrylamide gel electrophoresis (PAGE), capillary electrophoresis (CE), gel permeation chromatography (GPC), acid-base titration, nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and electrospray ionization (ESI) mass spectrometry. PAGE and CE studies showed that electrophoretic mobilities at pH 2.5 are in the order of E1.NH 2>E1.N(Gly)OH>E1.NHAc. Mass spectrometry and NMR investigations ( 1H, 13C DEPT-135, and 13C NMR, COSY, HETCOR, NOESY) suggested that (a) the studied E1 dendrimers were generationally pure, (b) E1.NHAc and E1.N(Gly)OH dendrimers, and essentially had the same defects and skeletal diversity as E1.NH 2 did. The broad distribution of the main peak in the CE electropherogram of E1.N(Gly)OH revealed the incomplete hydroxylation of E1.NH 2 resulting in additional substitutional diversity between the dendrimer molecules. Potentiometric titration studies proved that overall numbers of terminal and tertiary amine groups also deviated from the theoretical values. NMR spectroscopy was applied for both qualitative and quantitative analysis of the structural defects of dendrimers and derivatives. E1.NH 2 and E1.NHAc exhibited only minor deviations from ideal structures and, respectively, displayed a narrow distribution; while E1.N(Gly)OH had a much broader distribution centered around 14plusmn3 glycidol substituents. The study of structural variations in generation 1 PAMAMs provides new insights for the characterization of higher generation PAMAM dendrimers and derivatives both in terms of the skeletal deviations as well as other resulting diversities related to dendrimer surface functionalization. [All rights reserved Elsevier]
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  • Polyelectrolyte multilayer nanoreactors toward the synthesis of diverse nanostructured materials

    Xiangyang Shi   Mingwu Shen   Helmuth M?hwald  

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