Current Nanoscience - Volume 7, Issue 6, 2011
Volume 7, Issue 6, 2011
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Editorial [Hot Topics: The Prospects of Nanomaterials on Healthcare Technology (Guest Editor: Ming-Fa Hsieh)]
More LessThe traditional idea of dealing materials is to know the relationship among properties, process and microstructure. However, along the development of nanomaterials for medical applications, the research communities become aware of the sciences in nano-scale scenario [1,2]. Likewise, the interplay between nanomaterials and living organism is being unwinded using sophisticated methods and instruments [3,4]. In recent years, the revolution of healthcare technology is considered the most important topic for the elderly populations around the world. Furthermore, these efforts are being translated from the nano-science research to clinical applications for more effective and safe treatment in clinic setting [5,6]. This thematic issue covers the original articles reporting various morphologies of nanomaterials, including nanoparticles, nano-coating, nano-fibers, and membranes. H. Wang and K. Dimitrov described a novel method to conjugate immunoglobulin to gold nanoparticles. Because of good biocompatibility, hydroxyapatite(HAp) has been utilized not only in orthopedics [7]. H. C. Wu et al. prepared the nanocomposite of HAp and iron oxide which made the composite superparamagnetic for the application of magnetic resonance imaging. Y. C. Lin et al. showed that HAp-silk porous scaffold can promote the proliferation of bone marrow derived mesenchymal stem cells. Regarding thermal stability of HAp subject to high temperature sintering, S. Ramesh et al. reported that a pure nanocrystalline HAp could be sintered without a compromise of mechanical properties. Similarly, F. H. Lin et al. reported montmorillonite, a type of clay mineral that was found to adsorb bamboo vinegar. The composite was found to deactivate porcine reproductive and respiratory syndrome virus. Y. T. Yang et al. showed that cellular photodynamic toxicity of hematoporphyrin could be adjusted when hematoporphyrin was encapsulated in either nanosized polymeric micelles or liposomes. In the case of sub-cellular scenario, M. R. Rekha and C. P. Sharma reported the intracellular trafficking of non-viral gene vector made of polyethyleneimine-conjugated pullulan. In view of the two-dimensional nanostructure, M. Liu et al. displayed that nano-coating of polysaccharides can resist thrombogenecity leading to a safe coating on the surface of Nitinol stents. The nano-fibrous mat, made of biodegradable polyesters, resembles the extracellular matrix of PC-12 cell lines as depicted in S. F. Chang's article. In this way, better neurite outgrowth was observed. To further mimic natural structure of extracellular matrix, A. Higuchi et al. immobilized nano-segments of gelatin, laminin, fibronectin and vitronectin on the surface polystyrene. In this work, amniotic fluid stem cells could respond to different nano-segments and, therefore, differentiate into osteoblast or neural cells. Similarly, surface grafting of the nano-segments on polyurethane surface was found to separate hematopoietic stem cells. In the molecular scale, T. Hashimoto and M. Yoshikawa reported that the polyamide membrane with aspartyl moiety could also be used to perform chiral separation of racemic mixtures which are very common to the biological systems. In conclusion, the papers in the present issue encompass a wide range of materials science, say polymers, bioceramics and their composites. I hope you enjoy reading the articles in this issue. Thanks to the reviewers of this issue for improving the quality of the articles.
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The Effects of Montmorillonite and Bamboo Vinegar on Porcine Reproductive and Respiratory Syndrome Virus
Authors: Feng-Huei Lin, Ling-Ling Chueh, Yuan-Haun Lee and I-Shan HoEarly last year, Severe Acute Respiratory Syndrome (termed as SARS) heavily hit the entire Asia and caused a great panic all over the world. A number of agents with different formula have been developed to curb the epidemics. Bamboo vinegar (termed as Bv) is one of the effective agents to de-activate the bacteria. However, bamboo vinegar cannot stay longer (less than 15 min) on the spraying surface due to easy evaporation. In the study, we attempt to prove the ability of bamboo vinegar on virus deactivation and extend the function of bamboo vinegar for longer time. The special characteristics of montmorillonite and bamboo vinegar (termed as M+Bv) are utilized to adsorb virus and deactivate the virus from cell infection. The SARS virus is highly infective and hard to acquire, so we turn to the porcine reproductive and respiratory syndrome (PRRS) virus. The PRRS virus and SARS virus both belong to Nidovirales, and both are RNA viruses with envelope, having similar virus character. According to the results of electrophoresis diagram of reverse transcription polymerase chain reaction (RT-PCR) product proves that montmorillonite can adsorb PRRS virus and montmorillonite concentration of 25 mg/ml can totally adsorb 5 × 105 TCID50/ml PRRS virus. Bamboo vinegar has a good ability to deactivate PRRS virus and protect the MARC-145 cell from infection. The ability of bamboo vinegar to deactivate virus can be enhanced by montmorillonite. It is proven that co-cultures of M+Bv with virus (termed as M+Bv+V) have good result on PRRS virus deactivation and can extend the ability for 2 weeks or even longer. All the results can be proven by RTPCR, immunofluorescent assay, and transmission electron microscopy. PRRS virus belongs to the same category with SARS virus. The composite of montmorillonite and bamboo vinegar should have a great potential against SARS epidemics.
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Sintering Behavior of Nanocrystalline Hydroxyapatite Produced by Wet Chemical Method
Authors: S. Ramesh, R. Tolouei, M. Hamdi, J. Purbolaksono, C. Y. Tan, M. Amiriyan and W. D. TengThe sintering behavior of synthesized nanocrystalline hydroxyapatite (HA) powder was investigated in terms of phase stability and mechanical properties. A wet chemical precipitation method was successfully employed to synthesize a high purity and single phase HA powder. After shaping, HA powder compacts have been sintered over the temperature range of 1000°C to 1300°C. Two different sintering holding times of 1 minute and 120 minutes were investigated. The results revealed that the 1 minute holding time profile was effective in suppressing grain growth and producing a HA body with improved densification. Additionally, higher mechanical properties such as Young's modulus of 119 GPa, high fracture toughness of 1.41 MPa.m1/2 and hardness of 9.5 GPa were obtained for this sample as compared to HA bodies when sintered using the 120 minutes holding time. The study revealed for the first time that HA could be sintered using a 1 minute holding time without compromising on HA phase stability and mechanical properties.
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Cellular Photodynamic Toxicity of Hematoporphyrin in Various Nanocarrier Systems
Authors: Yu-Tsai Yang, Chin-Tin Chen, Hsiung-Fei Chien and Tsuimin TsaiIn this study, we investigated the cellular uptake of Hematoporphyrin (Hp) encapsulated in nanocarriers by human lung adenocarcinoma A549 cells and the photodynamic toxic effects on those cells. The nanocarriers included liposomes, micelles, and nanoparticles. The Hp was encapsulated in liposomes through a film hydration and extrusion method. Hp was encapsulated in micelles through a film hydration method. The Hp loaded nanoparticles were prepared using an emulsification-diffusion process. The Hp in nanocarriers was characterized by laser light scattering to determine particle size and zeta potential of the surface charge. The cellular uptake of nanocarriers was measured by fluorescence spectrometry. The photodynamic toxicity of various Hp nanocarriers was evaluated in human lung epithelial carcinoma A549 cells using a light-emitting diode (LED) device at a wavelength of 630± 5 nm. The averaged size of all nanocarriers was between 112 and 135 nm. The surface charge observed for all formulations, particularly the micelles showed lower negative valued than those of other systems. Cellular uptake and photocytotoxicity of the four Hp preparations in serum free medium were in the following order: micelle-Hp > nanoparticle-Hp > liposome-Hp > free Hp. In the presence of serum protein, the photodynamic toxicity of all formulations significantly decreased.
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Nanocoating of Diazoresin/Polysaccharides Multilayer Boosts Biocompatibility of Nitinol Biomedical Devices
Authors: Meng Liu, Xiuli Yue, Shen Dong, Yan Ma, Zhengbao Zha and Zhifei DaiThe surface of a biomaterial and a biological environment are key factors determining the biocompatibility of the material. Determining biocompatibility of medical implants is a critical step toward approval and clinical application. In this study, the biocompatibility of a covalently attached nanocoating of alginate(Alg)/diazoresin(DR)/heparin(Hep) multilayer has been evaluated by thrombin inactivation, protein adsorption, leukocyte adhesion, cytotoxicity in vitro and subcutaneous implantation in vivo. It was found that the outermost layer of the coating played a key role on anticoagulant activity. No significant difference was seen in albumin adsorption between uncoated and coated one. However, the fibrinogen adsorption on DR/polysaccharides coatings was lower than the uncoated Nitinol. Compared with the uncoated Nitinol surface, DR/polysaccharides multilayer coating presented a drastically reduced adhesion in vitro of polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC). Cell biocompatibility tests indicated that the nanocoating of DR/polysaccharides multilayer did not lead to an increase in the cytotoxicity of the Nitinol and the adherent cells maintained good viability. Subcutaneous implantation in C57BL/6 mice suggested that the coated Nitinol had good tissue biocompatibility. The use of alginate interlayer for heparin immobilization instead of proteins such as albumin, collagen, and gelatin may avoid the risk of contamination with pathogenic agents. Hence, the nanocoating of covalently attached DR/polysaccharide multilayer boosts the biocompatibility of Nitinol biomedical devices.
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Synthesis and Characterization of Hydroxyapatite-Silk Composite Scaffold for Bone Tissue Engineering
Authors: Yen-Chih Lin, Thomas K.H. Teh and James C.H. GohChallenges persist in the restoration of tibial and femoral defects caused by anterior cruciate ligament (ACL) reconstruction surgery. Since one of the major inorganic components of bone tissue is hydroxyapatite (HA), we hypothesize that the implantation of HA-modified silk (HA-silk) scaffolds can promote osteogenesis in the tibial and femoral defects. This study focuses on evaluating and characterizing the HA-silk scaffolds fabricated with two different techniques: coated HA (HA-coated) and cross-linked with HAnanoparticles encapsulated microspheres (HA-microspheres), with the aim of determining the optimal form for HA-silk porous scaffolds for this application. Results show that the mean diameter of HA-microspheres ranges from 200 μm to 280 μm. Swelling ratio measurements reveal that all specimens can absorb 3-4 folds of physiological fluid with their form and stability maintained. In terms of mechanical attributes, HA-silk scaffolds exhibit significantly improved mechanical properties compared to pure silk scaffolds. In vitro culture results with bone marrow derived mesenchymal stem cells (BMSCs) show that the HA-silk scaffolds supported cell viability and proliferation as the HA-silk scaffolds have significantly more cells (2.20-3.45 × 105 cells/scaffold) than the pure silk scaffolds (1.5 × 105 cells/scaffold) after 14 days (p<0.05). Bone tissue-specific gene transcription for osteonection, osteopontin and collagen (types I, II, and III) detected via quantitative real-time RT-PCR show a significant up-regulation of osteonectin and osteopontin in HA-silk scaffolds by 2.5-3.7 and 1.7-2.3 folds respectively compared to undifferentiated BMSCs (p<0.05). Histological observations indicate uniform cellular deposition and mineralization in the HA-silk scaffolds. From the results, it is indicative that the HA-silk scaffolds, especially that with nanoparticular HA-microspheres of high HA content (500 mg), are suitable for bone tissue engineering applications.
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Conjugation of Immunoglobulin M to Gold Nanoparticles
Authors: Hui Wang and Krassen DimitrovDue to unique optical properties, facile bioconjugation, and biocompatibility, colloidal gold nanoparticles have been widely used for nuclear targeting, gene and drug delivery, and biomedical diagnosis and therapeutics. Various peptides, proteins, and polymers, etc. have been utilized to functionalize gold nanoparticles. Especially antibodies-AuNPs conjugates have drawn more and more attractions due to their specific affinities to the target antigens. However, to our best knowledge, immunoglobulin M (IgM) has not been applied for AuNPs modification so far. In this work, we present a simple modification process to immobilize IgM on the surface of gold nanoparticles. Dark field microscopy, light scattering, and colorimetric assays were conducted to monitor the conjugation process. The properties of AuNPs before and after IgM modification were further studied. The results demonstrated that the stability of AuNPs was improved upon IgM conjugation. This study may open a new way to apply IgM conjugated AuNPs for biomedical potential applications.
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Intracellular Trafficking Mechanism and Cytosolic Protein Interactions of a Non Viral Gene Delivery Vector: Studies Based on Transferrin Conjugated Pullulan-PEI
Authors: Rekha M.R. and Chandra P. SharmaCompared to viral vectors the intracellular barriers faced by non-viral vectors are high, which lead to lesser transfection efficiency. The various limiting steps include endocytosis, endosomal escape, intracellular stability and mobility, unpacking and nuclear localization. The understanding of these mechanisms for overcoming these barriers is essential for developing gene delivery vectors which can really be used for appropriate clinical/medical applications. Transferrin conjugated pullulan-PEI (PPETf) was developed for neuronal cell targeted gene delivery which was evaluated for its transfection efficiency. The stability of the polymer-DNA nanoplexes in the presence of plasma and cytosolic proteins was evaluated by agarose gel electrophoresis. Time dependent uptake of the nanoplexes by using labeled polymer and YOYO tagged plasmid was employed to understand the uptake mechanism and the sequence of unpacking of DNA from the vector. The uptake pathway, endosomal escape, trafficking etc. are evaluated in the presence of endocytic and microtubilin inhibitors to understand the mechanism of nanoplexes trafficking into and within the cell.
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Gene Expression and Behavior Analysis of PC12 Cells Grown on Biodegradable Nano-fibrous Membranes
Authors: Shwu-Fen Chang, Chih-Ping Yang, Chien-Cheng Tai and How TsengThe use of biodegradable synthetic polyesters as peripheral nerve conduits and the “contact guidance” effect of nano-sized fibrous matrices on neurite outgrowth have been reported; however, no literature exists regarding how these matrices regulate neurite growth-related gene expression. Such information would be useful in the evaluation of the biological applicability of various materials. In this study, two biodegradable synthetic polyesters (PLLA and PBSA) were employed to fabricate a series of micro/nano-fibrous membranes that were used as culture matrices for the in vitro growth of PC12 cells in response to nerve growth factor (NGF). Cell adhesion, proliferation, and differentiation were analyzed in addition to neurite outgrowth- and apoptosis-related gene expression. Our results show that cells grown on electrospun PBSA membranes proliferate to a greater extent than cells cultured on tissue culture polystyrene (TCPS) and other prepared membranes. Compared to TCPS and PBSA, growth on an electrospun PLLA membrane triggers higher GAP43 and MAP2 gene expression in PC12 cells. No significant effect of membrane type on apoptosis-related gene expression was observed. These results indicate that electrospun nano-fibrous PLLA mats are more suitable for use as nerve conduit matrices than conventional non/micro-fibrous PLLA or PBSA membranes.
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Differentiation Ability of Amniotic Fluid-Derived Stem Cells Cultured on Extracellular Matrix-immobilized Surface
Stem cells from amniotic fluid were cultured on dishes coated or grafted with extracellular matrix (ECM) or Matrigel where gelatin, collagen, fibronectin, laminin, and vitronectin were selected as ECM components (nanosegments). The effects of interactions between amniotic fluid stem cells and nanosegments were investigated on the expression of surface markers of mesenchymal stem cells and on the differentiation abilities of osteoblasts and neural cells. The ECM-coated dishes produced water contact angles from 35 to 65 degrees, whereas ECM-grafted dishes produced water contact angles from 50 to 70 degrees, which was an adequate water contact angle range for our cell culture conditions. Culture on ECM-immobilized dishes enhances amniotic fluid stem cell differentiation into osteoblasts more than culture on polystyrene dishes grafted with amino groups (PS-NH2 dishes). This finding indicates that specific interactions between amniotic fluid cells and the ECM grafted onto the culture dishes promote the differentiation of cells into osteoblasts. Matrigel- immobilized dishes promoted a more extensive differentiation of amniotic fluid stem cells into neural cells than did ECMimmobilized dishes, but they did not promote differentiation into osteoblasts. Immobilization of the optimal nanosegments (ECM or Matrigel) onto culture dishes enhances amniotic fluid stem cell differentiation into osteoblasts and neural cells; the choice of nanosegments depends on the desired differentiated cell type.
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Characterization of Magnetic Hydroxyapatite Nanocrystallites and Potential Application for MRI Contrast Agent
Authors: Hsi-Chin Wu, Tzu-Wei Wang, Feng-Huei Lin and Jui-Sheng SunIn this study, synthetic hydroxyapatite nanoparticles (Hap NPs) were rendered magnetic by treatment with iron ions using a wet-chemical process. The magnetized Hap (mHap) NPs were fabricated by the addition of iron precursor in various ratios of Fe:Ca (XFe/ Ca). The physicochemical properties of mHap NPs were evaluated respectively, by X-ray diffraction (XRD) for the crystal structure, Fourier transform infrared (FTIR) spectroscopy for functional groups detection, Energy-Dispersive X-ray Spectroscopy (EDS) for composition analysis , transmission electron microscopy (TEM) for particle morphology characterization, and superconducting quantum interference device (SQUID) for magnetization property. The size distribution of mHap randomly in rod and needle-like shape was in average 80 to 120 nm. We found that the mHap was the result of the hetero-epitaxial growth of magnetite on the Hap crystallites. The magnetic NPs with sphere shape less than 10 nm in diameters were tightly surrounded on Hap crystallites and possessed superparamagnetic property. The magnetization of all groups of mHap NPs increased with the increasing of XFe/ Ca and with no toxic effect to cultured cells. In brief, mHap NPs demonstrated suitable physicochemical properties and good biocompatibility, suggesting that these NPs have potential applications as new biodegradable MRI contrast agent in medicine.
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Separation and Cultivation of Hematopoietic Stem Cells from Umbilical Cord Blood by Permeation through Membranes with Nano-Segments
Authors: Akon Higuchi, Li-Ying Chen, Jui-Shiang Shiao, Qing-Dong Ling, Yi-An Ko, Yung Chang, Yu Chang, Jun-Tang Bing and Shih-Tien HsuThe direct ex vivo expansion of hematopoietic stem cells (HSCs) extracted from umbilical cord blood (UCB) was investigated by a membrane filtration method using polyurethane foaming (PU) membranes with various nano-segments and pore sizes. After filtering UCB through the membranes and washing the membranes, the membranes were placed into culture medium, where the HSCs were expanded in a three-dimensional environment. The greatest expansion of HSCs was obtained through direct ex vivo expansion using PU membranes with nano-segments containing carboxylic acid. The membranes with larger pores (11 μm) exhibited greater expansion of HSCs than the membranes with smaller pores (6 μm), the membranes with nano-segments or unmodified membranes. The optimal pore size of the membranes was found to be regulated by the balance between the surface area required to trap HSCs and the diffusion potential of nutrition and growth factors, with a pore size of 11-100 μm proving most effective in the direct ex vivo expansion method. HSCs expanded by the direct ex vivo expansion method retained the same pluripotency as HSCs purified by the conventional Ficoll-Paque method, followed by the MACS method, as measured by the colony-forming assay. The optimal washing solution for the membranes was also investigated, using diluted platelet-poor plasma with phosphate buffered solution for the direct ex vivo expansion of HSCs.
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Chiral Separation of Racemic Mixtures with Chiral Polyamide Membranes Containing Aspartyl Residues in their Main Chains
Authors: Takeshi Hashimoto and Masakazu YoshikawaNovel chiral polyamides with chiral environment in their main chains were obtained from aromatic diamines, such as 1,3- phenylenediamine (1,3-PDA) or 1,4-phenhylenediamine (1,4-PDA), and the D-isomer or L-isomer of N-α-protected aspartic acid, such as N-α-benzyloxycarbonyl-D-aspartic acid (Z-D-Asp-OH) or N-α-benzyloxycarbonyl-L-aspartic acid (Z-L-Asp-OH), in the presence of triphenyl phosphite (TPP). Four types of newly prepared polyamide showed optical rotation, implying that there were asymmetric carbons in their main chains. CD studies demonstrated that resulting chiral polyamides took a helical structure. Surface plasmon resonance (SPR) spectroscopy studies revealed that the polyamide from Z-D-Asp and 1,4-PDA (1,4-PDA-Z-D-Asp) incorporated the L-isomer of glutamic acid (Glu) in preference to D-Glu and the adsorption selectivity toward L-Glu was determined to be 1.30 and vice versa; in other words, D-Glu was selectively adsorbed in 1,4-PDA-Z-L-Asp with the adsorption selectivity toward the D-isomer of 1.22. Contrary to the adsorption phenomena of the chiral polyamides consisting of 1,4-PDA, two types of 1,3-PDA-Z-Asp polyamide hardly showed adsorption selectivity toward racemic Glu. Chiral separation ability of those four types of polyamide was investigated by adopting concentration gradient or applied potential difference as a driving force for membrane transport. Membranes from chiral polyamide with 1,4-PDA as a diamine component showed permselectivity toward racemic mixture of Glu. The permselcetivity was dependent not only on the absolute configuration of diacid component but also on the nature of medium containing racemic mixture. In the enantioselective electrodialysis in an aqueous ethanol system, the permselectivity toward L-Glu for 1,4-PDA-Z-D-Asp membrane was determined to be 1.52 and that toward D-Glu for 1,4-PDA-Z-L-Asp membrane to be 1.77.
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Editorial [The Expectancy of Nanomaterials in Biomedical Application (Guest Editor: Ching-Li Tseng)]
More LessIn a rapidly developing field of nanotechnology, it is difficult to predict when this field will arrive at what mature endpoint. Today, nanomaterials are making significant advances in three broad areas: novel materials synthesis, superior cell imaging, and accurate biological assays. The interdisciplinary research involved in nanomaterials for biomedical application, such as drug delivery, cellular imaging and diagnostic applications etc. are promptly rising and prospering. This thematic issue covers the original articles reporting various types of nanomaterials, such as nano-fibers, nanoparticles for biosensor, molecular image and nanocarriers for drug transportation. In the view of nanomaterials for drug delivery, C. L. Tseng et al. show that the chemodrug, cisplatin, encapsulated in gelatin nanoparticles could be slowly released to cause toxicity reducing and have a superior anticancer effect in subcutaneous mice model. For a lethal infection disease, leishmaniasis (Kala-Azar) treatment, N. C. Mishra reports that electrospuned nanofibers with Amphotericin B loading could be highly promising for the treatment of Kala-Azar via controlled release effect. J. I. Kim et al. describe a ring open method to prepare a novel tri-copolymers, polyester-PPG-polyester, and shows that micelles could be formed by the tri-copolymers and may be a potential hydrophobic drug carrier. R. Moriyama et al. synthesized metylated PLL-g-Dex copolymer (MPLL-g-Dex); they investigated the interaction of copolymer with DNA and described unique properties of MPLL-g-Dex-DNAs which were linked by not only ionic but also hydrophobic interactions. To maintain the function of primary hepatocytes culture, two different engineered type I collagen, nano-sized one and anti-oxidative one were tested in the report of C. W. Lan's study. The result shows that nano-sized collagen could facilitate cell aggregation and formation of hepatic spheroids; the addition of anti-oxidative collagen could facilitate the maintenance of the gene expression of Cytochrome P450 of hepatocytes. S. M. Kuo et al. also investigate how type I and type II collagen nano-spheres influence hepatocytes and chondrocytes cultures. In this work, hepatocytes and chondrocytes cultured with collagen nano-spheres could rapidly form cell pellets, maintaining their in vivo-like morphologies and specific functions....
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Facile Synthesis of Hollow Mesoporous Hydroxyapatite Nanoparticles for Intracellular Bio-imaging
Authors: Kevin C.-W. Wu, Ya-Huei Yang, Yung-He Liang, Hui-Yuan Chen, Eric Sung, Yusuke Yamauchi and Feng-Huei LinThe effects of several critical factors including the amount of EG, the reaction time, the concentrations of Ca(CH3COO)2 and NaHCO3, the concentration of H3PO4, and the amount of acetic acid were investigated for synthesizing hollow mesoporous hydroxyapatite nanoparticles (hm-HANPs). We optimized the reaction conditions as follows: the concentration of Ca(CH3COO)2 and NaHCO3 was 0.3 M, the ratio of Ca(CH3COO)2 and NaHCO3 to ethylene glycol (EG) was 1:5, the reaction time for the formation of hydroxyapatite was 3 hr, the concentration of H3PO4 was 0.01 M, and the ratio of hm-HANP solution to acetic acid was 1:3.125. Monodispersed hm- HANPs with a defined particle size could be obtained. A fluorescent dye named fluorescein isothiocyanate (FITC) was successfully linked to the surface of hm-HANPs for the bioimaging of hm-HANPs in living breast cancer cells (BT-20). The FITC-hm-HANPs were taken up by the cells and stayed in the cytoplasm with high biocompatibility. The information obtained in this study will benefit the synthesis of hydroxyapatite nanostructures for many biomedical-related applications.
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Preparation and Characterization of Cisplatin-Incorporated Gelatin Nanocomplex for Cancer Treatment
Authors: Ching-Li Tseng, Kai-Chiang Yang, Ko-Chung Yen, Steven Yueh-Hsiu Wu and Feng-Huei LinTo develop a polymer-anticancer drug conjugate accompanied by a reduction of anticipated side effects and therapeutic improvement, we employed gelatin nanoparticles (GPs) as carriers for cisplatin (CDDP). The GPs-cisplatin nanocomplex (GP-Pt) was fabricated by a two-step desolvation process from gelatin type A. The parameters for the optimal GP-Pt preparation were investigated, including temperature, the pH of the gelatin solution, glutaraldehyde (GA) concentration, and the time point for CDDP addition. GP-Pt was characterized by its size, surface charge, morphology, and drug release rate. The chemical and physical properties of GP-Pt have been studied using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), and thermal gravimetric analysis (TGA). In vivo anticancer effects and reductions in toxicity were evaluated by intratumorally injecting GP-Pt into SCID mice that had been injected with human lung carcinoma cells (A549 cells) as a subcutaneous cancer model. The GP-Pt prepared with gelatin type A solution at pH 2.5 with a 0.4 % GA addition achieved the smallest size. The FT-IR assay result showed that GPs conjugated with cisplatin via an ion-exchange of the carboxyl group of the gelatin. In vivo anticancer effects were revealed in that GP-Pt could effectively decrease the tumor size, and mice treated with GP-Pt lived longer than those treated with free CDDP, which indicates reduced toxicity due to cisplatin. The systematic investigation of the synthesis parameters showed that it is possible to prepare GPs with a small size distribution and with the incorporation of high cisplatin. We showed that the GP-Pt nanocomplex was less toxic than the free drug, and that it could effectively reduce the tumor size and toxic effects in mice grafted with A549 cells. The results of this study suggest that GP-Pt could be slowly released to reduce the toxicity of cisplatin, and that it may be used as a potential drug delivery system for chemotherapy.
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Effects of Collagen Nano-Spheres on Cell Cultures
Authors: Shyh Ming Kuo, Shwu Jen Chang, Cheng-Wen Lan, Yueh-Sheng Chen, Guo-Chung Dong and Chun-Hsu YaoA conventional means of repairing a damaged organ or tissue is to introduce cultured cells or tissues to the corresponding defect site. Three factors affecting the success of such repair include cell culturing, scaffolding and the signaling factors between the cells and scaffold. Enhanced binding of cell adhesion molecules, such as integrin, to specific molecules of the extracellular matrix (such as RGD sequences on the collagen) can generally induce cytoplasmic signal transduction cascades and activate gene expressions, subsequently achieving rapid cell proliferation and differentiation. This study investigates how type I and type II collagen nano-spheres in the culture medium influence hepatocytes and chondrocytes cultures. Experimental results indicate that hepatocytes demonstrated better viability and function after adding a higher concentration of type I collagen nano-spheres (5x10-2 mg/ml) to the culture medium than with lower concentration collagen particles (5x10-4 mg/ml) and the control group. The hepatocytes cultured with type I collagen nano-spheres also had a slightly higher level of albumin secretion in static dish cultures than that of the control group. Additionally, hepatocytes cultured in a stir bioreactor by adding type I collagen nano-spheres for 5 days formed a cell spheroid that is approximately 5 mm in diameter. In chondrocytes cultures, the chondrocytes displayed a higher secretion of glucosaminoglycan (GAG) than that of the control group (without adding collagen nano-spheres). Chondrocytes could form a large amount of spheroids rapidly with adding type II collagen nanospheres to the medium in a 1-day rotary bioreactor culture. Histological staining and SEM observations revealed that these chondrocytes still retained their original phenotype and secreted collagen around the cells. In summary, hepatocytes and chondrocytes cultured in a rotary bioreactor while adding a moderate concentration of collagen nano-spheres could rapidly form cell pellets, maintaining their in vivolike morphologies and specific functions.
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“Amphotericin B” Loaded Natural Biodegradable Nanofibers as a Potential Drug Delivery System against Leishmaniasis
Authors: Himansu Sekhar Nanda and Narayan Chandra MishraDrug loaded nanofibers were prepared as a novel drug delivery system for the delivery of a medical drug-Amphotericin B which is the most promising drug for leishmaniasis (Kala-Azar). The nanofibers were prepared from 10 wt. % gelatin in acetic acid and water mixed with 1 wt. % Amphotericin B, and the fiber-morphology was studied by the Field Emission Scanning Electron Microscopy (FE-SEM). The formation of bead-free fibers was observed with an average diameter of 100nm, at optimal process conditions. The chemical integrity of the drug in the electrospun nanofibers, was confirmed by Fourier Transformation Infra Red (FTIR) spectroscopic analysis. The release of the Amphotericin B from the nanofibers, was investigated by UV-Visible spectrophotometer in phosphate buffer of pH 7.4 at normal physiological body temperature of 37°C. A controlled pattern for the release of Amphotericin B from the gelatin nanofibers, was observed — suggesting electrospun Amphotericin B loaded biodegradable nanofibers to be highly promising for the treatment of leishmaniasis (Kala-Azar).
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Hydrophilic Modification of Au Nanoparticles on the Gold Electrode of QCM by Plasma Deposition for Biomedical Applications
Authors: Tsui-Hsun Wu, Shu-Chuan Liao, Yi-Shiuan Wei, Shu-Ju Tu, Yi-You Huang, Hsin-Ming Wu and Ko-Shao ChenIn this study, we proposed a method of surface modification for gold nanoparticles (AuNPs) for biomedical research and applications. 11-Mercaptoundecanoic acid (MUA) is a hydrophilic material and was used to modify the surface on AuNPs by self-assembly mechanism to promote the hydrophilic property and decrease water contact angle (WCA) by 3.2°. To measure the mass of modified AuNPs, the surface of gold electrodes of QCM (quartz crystal microbalance) was plasma-deposed with Hexamethyldisilazane (HMDSZ) and O2 by the plasma deposition method at the condition of low temperature. The content of AuNPs was determined by the relation between frequency shift and concentration of AuNPs. This study showed that the gold electrode surface became hydrophobic after HMDSZ deposition treatment. Also the WCA of the surface of gold electrode decreased to less than 10° and hydrophilic property after O2 treatments were detected, compared to the HMDSZ treatment alone. The surface of gold electrode was treated by both HMDSZ and O2 procedures. The sensitivity of QCM measurement for the AuNPs could be improved and have a good linear relationship (R2:0.9722). In vitro study, there was no cytotoxicity of MUA-AuNPs in the MTT assay and cell uptake was quantified by the micro CT imaging. Our proposed method offered a new method for immobilized biomolecular coating for AuNPs and biosensor.
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Ring-Opening Polymerization of Cyclic Ester Monomers by Poly(propylene glycol) in the Presence of Monomer Activator and Examination of Triblock Copolymer Solution Properties
Authors: Jae Il Kim, Hwi Ju Kang, Doo Yeon Kwon, Bong Lee, Heung Jae Chun, Jae Ho Kim and Moon Suk KimThe ring-opening polymerization of ε-caprolactone (CL), δ-valerolactone (VL), and trimethylene carbonate (TMC) was carried out with polypropylene glycol (PPG) as an initiator in the presence of the monomer activator HCl to synthesize various polyesterpoly( propylene glycol)-polyester triblock copolymers (polyester-PPG-polyester). The resultant polyester-PPG-polyester triblock copolymers had molecular weights close to theoretical values. The formation of polymeric micelles from these triblock copolymers in aqueous media was confirmed by NMR, dynamic light scattering, and fluorescence techniques. The critical micelle concentrations (CMC) of the polyester-PPG-polyester triblock copolymers ranged from 1.7 x 10-3 to 2.1 x 10-3 mg/mL. The partition equilibrium constants illustrated the hydrophobicities of the polyester cores of the polyester-PPG-polyester triblock copolymers. In conclusion, we confirmed that the polyester-PPG-polyester triblock copolymers formed micelles and hence may be potential hydrophobic drug carriers.
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Volumes & issues
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Volume 21 (2025)
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Volume 20 (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)
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