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Macromolecular Bioscience

Claudia Battistella, Harm-Anton Klok
Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer-based nanocarriers allow to increase plasma half-life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well-defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm...
April 26, 2017: Macromolecular Bioscience
Doreen Hentrich, Soraya Taabache, Gerald Brezesinski, Nele Lange, Wolfgang Unger, Christian Kübel, Annabelle Bertin, Andreas Taubert
The phase behavior of a dendritic amphiphile containing a Newkome-type dendron as the hydrophilic moiety and a cholesterol unit as the hydrophobic segment is investigated at the air-liquid interface. The amphiphile forms stable monomolecular films at the air-liquid interface on different subphases. Furthermore, the mineralization of calcium phosphate beneath the monolayer at different calcium and phosphate concentrations versus mineralization time shows that at low calcium and phosphate concentrations needles form, whereas flakes and spheres dominate at higher concentrations...
April 18, 2017: Macromolecular Bioscience
Mathias Dimde, Fitsum Feleke Sahle, Virginia Wycisk, Dirk Steinhilber, Luis Cuellar Camacho, Kai Licha, Jürgen Lademann, Rainer Haag
In the present study, a pH responsive dendritic polyglycerol nanogel (dPG-NG) is developed to measure the pH values inside the hair follicle (HF) using an ex vivo porcine ear model. The macromolecular precursors are labeled with a pH sensitive indodicarbocyanine dye (pH-IDCC) and a control dye (indocarbocyanine dye: ICC) and crosslinked via a mild and surfactant-free Thiol-Michael reaction using an inverse nanoprecipitation method. With this method, it is possible to prepare tailor-made particles in the range of 100 nm to 1 µm with a narrow polydispersity...
April 10, 2017: Macromolecular Bioscience
Jin Kim, Kisuk Yang, Jong Seung Lee, Yong Hwa Hwang, Hyun-Ji Park, Kook In Park, Dong Yun Lee, Seung-Woo Cho
Graphene oxide (GO) has received increasing attention in bioengineering fields due to its unique biophysical and electrical properties, along with excellent biocompatibility. The application of GO nanoparticles (GO-NPs) to engineer self-renewal and differentiation of human fetal neural stem cells (hfNSCs) is reported. GO-NPs added to hfNSC culture during neurosphere formation substantially promote cell-to-cell and cell-to-matrix interactions in neurospheres. Accordingly, GO-NP-treated hfNSCs show enhanced self-renewal ability and accelerated differentiation compared to untreated cells, indicating the utility of GO in developing stem cell therapies for neurogenesis...
April 10, 2017: Macromolecular Bioscience
Sandro Sieber, Stefan Siegrist, Stéphanie Schwarz, Fabiola Porta, Susanne H Schenk, Jörg Huwyler
Enzyme immobilization is of high interest for industrial applications. However, immobilization may compromise enzyme activity or stability due to the harsh conditions which have to be applied. The authors therefore present a new and improved crosslinked layer-by-layer (cLbL) approach. Two different model enzymes (acid phosphatase and β-galactosidase) are immobilized under mild conditions on biocompatible, monodisperse, sub-micrometer poly(lactide-co-glycolide) (PLGA) particles. The resulting PLGA enzyme systems are characterized regarding their size, surface charge, enzyme activity, storage stability, reusability, and stability under various conditions such as changing pH and temperature...
April 7, 2017: Macromolecular Bioscience
Mahsa Jamadi, Parvin Shokrollahi, Behzad Houshmand, Mortaza Daliri Joupari, Fatemeh Mashhadiabbas, Ali Khademhosseini, Nasim Annabi
Tissue expansion is used by plastic/reconstructive surgeons to grow additional skin/tissue for replacing or repairing lost or damaged soft tissues. Recently, hydrogels have been widely used for tissue expansion applications. Herein, a self-inflating tissue expander blend composition from three different molecular weights (2, 6, and 10 kDa) of poly (ethylene glycol) diacrylate (PEGDA) hydrogel with tunable mechanical and swelling properties is presented. The in vitro results demonstrate that, of the eight studied compositions, P6 (PEGDA 6 kDa:10 kDa (50:50)) and P8 (PEGDA 6 kDa:10 kDa (35:65)) formulations provide a balance of mechanical property and swelling capability suitable for tissue expansion...
April 6, 2017: Macromolecular Bioscience
Matthias Bartneck
Immunity has a major impact on inflammatory diseases and cancer, and biologics targeting immune cells and their factors reach a quarter trillion of market volume by this year. Adaptive leukocytes have recently been engaged in cancer immunotherapy, whereas modulation of the innate immune cells, specifically macrophages, is expected as next breakthrough. With patents of major biologics expiring, nanomedicine has the potential to substitute therapeutic proteins by using miniaturized macromolecules. This review includes an overview on the involvement of major immune cell types into disease and a summary on selected current therapies based on biologics and small molecules...
April 6, 2017: Macromolecular Bioscience
Jee-Wei Emily Chen, Sara Pedron, Brendan A C Harley
Glioblastoma (GBM) is the most common and lethal form of brain cancer. Its high mortality is associated with its aggressive invasion throughout the brain. The heterogeneity of stiffness and hyaluronic acid (HA) content within the brain makes it difficult to study invasion in vivo. A dextran-bead assay is employed to quantify GBM invasion within HA-functionalized gelatin hydrogels. Using a library of stiffness-matched hydrogels with variable levels of matrix-bound HA, it is reported that U251 GBM invasion is enhanced in softer hydrogels but reduced in the presence of matrix-bound HA...
April 5, 2017: Macromolecular Bioscience
Amaya Niño-Pariente, Ana Armiñán, Sören Reinhard, Claudia Scholz, Ernst Wagner, María J Vicent
Due to the polyanionic nature of DNA, typically cationic or neutral delivery vehicles have been used for gene delivery. As a new approach, this study focuses on the design, development, and validation of nonviral polypeptide-based carriers for oligonucleotide delivery based on a negatively charged poly-l-glutamic acid (PGA) backbone partly derivatized with oligoaminoamide residues. To this end, PGA-derivatives modified with different pentameric succinyl tetraethylene pentamines (Stp5 ) are designed. Optionally, histidines for modulation of endosomal buffer capacity and cysteines for pDNA complex stabilization are included, followed by characterization of biophysical properties and gene transfer efficiency in N2a neuroblastoma or 4T1 breast cancer cells...
April 5, 2017: Macromolecular Bioscience
Alan R Mackie, Francisco M Goycoolea, Bianca Menchicchi, Carla Marcella Caramella, Francesca Saporito, Seunghwan Lee, Karen Stephansen, Ioannis S Chronakis, Marianne Hiorth, Malgorzata Adamczak, Max Waldner, Hanne Mørck Nielsen, Luciano Marcelloni
The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented...
April 5, 2017: Macromolecular Bioscience
Shanmei Yuan, Jisong Hua, Yinyin Zhou, Yin Ding, Yong Hu
Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W18 O49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W18 O49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment...
April 4, 2017: Macromolecular Bioscience
Christoph Englert, Michael Pröhl, Justyna A Czaplewska, Carolin Fritzsche, Elisabeth Preußger, Ulrich S Schubert, Anja Traeger, Michael Gottschaldt
The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography...
April 3, 2017: Macromolecular Bioscience
Alaa S Abd-El-Aziz, Christian Agatemor, Nola Etkin, Rabin Bissessur, David Overy, Martin Lanteigne, Katherine McQuillan, Russell G Kerr
New macromolecules such as dendrimers are increasingly needed to drive breakthroughs in diverse areas, for example, healthcare. Here, the authors report hybrid antimicrobial dendrimers synthesized by functionalizing organometallic dendrimers with quaternary ammonium groups or 2-mercaptobenzothiazole. The functionalization tunes the glass transition temperature and antimicrobial activities of the dendrimers. Electron paramagnetic resonance spectroscopy reveals that the dendrimers form free radicals, which have significant implications for catalysis and biology...
March 31, 2017: Macromolecular Bioscience
Ines Truebenbach, Jan Gorges, Jasmin Kuhn, Sarah Kern, Emanuele Baratti, Uli Kazmaier, Ernst Wagner, Ulrich Lächelt
The conjugation of small molecule drugs to ligand containing carrier systems facilitates receptor targeted delivery. The folate receptor (FR) constitutes an ideal target for tumor selective therapy, being overexpressed on several tumor types. It can be targeted using the vitamin folic acid (FolA) or the structurally related drug methotrexate (MTX). Several sequence-defined oligoamides with mono- and multivalent FolA or MTX ligands and an additional thiol conjugation site are synthesized via solid-phase assisted synthesis...
March 30, 2017: Macromolecular Bioscience
Li Zhang, Dongjian Shi, Chunling Shi, Liangliang Dong, Xiaojie Li, Mingqing Chen
Novel biodegradable polymers with specific properties, structures, and tailorable designs or modifications are in great demand. Poly(phosphoester)s with good biocompatibility and degradability, as well as other adjustable properties have been studied widely because of their potential in biomedical applications. To meet more versatile and diverse biomedical applications, a novel multiarm star-shaped phosphorester triblock copolymer poly(amido amine)-block-poly(2-butynyl phospholane)-block-poly(2-methoxy phospholane) (PAMAM-PBYP-PMP) is synthesized via organo-catalyzed sequential ring-opening polymerization...
March 29, 2017: Macromolecular Bioscience
Lia Appold, Yang Shi, Stephan Rütten, Alexander Kühne, Andrij Pich, Fabian Kiessling, Twan Lammers
Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. In recent years, MB have also attracted interest as drug delivery systems. Soft-shelled lipidic MB tend to be more advantageous for US imaging, while hard-shelled polymeric MB appear to be more suitable for drug delivery purposes because of their thicker shell and the resulting higher drug loading capacity. The physicochemical composition of the shell of polymeric MB, however, remains largely unknown. This study sets out to evaluate the molecular weight and polydispersity of the building blocks constituting the shell of poly(butyl cyanoacrylate) (PBCA) MB...
March 29, 2017: Macromolecular Bioscience
Saltuk B Hanay, Bas Ritzen, Dermot Brougham, Aylvin A Dias, Andreas Heise
Highly efficient functionalization and cross-linking of polypeptides is achieved via tyrosine-triazolinedione (TAD) conjugation chemistry. The feasibility of the reaction is demonstrated by the reaction of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) with tyrosine containing block copolymer poly(ethylene glycol)-Tyr4 as well as a statistical copolymer of tyrosine and lysine (poly(Lys40 -st-Tyr10 )) prepared form N-carboxyanhydride polymerization. Selective reaction of PTAD with the tyrosine units is obtained and verified by size exclusion chromatography and NMR spectroscopy...
March 29, 2017: Macromolecular Bioscience
Guoqing Yan, Jun Wang, Jiejie Qin, Liefeng Hu, Panpan Zhang, Xin Wang, Rupei Tang
To compare the chemotherapeutic efficacy determined by extra- and intracellular drug release strategies, poly(ortho ester amide)-based drug carriers (POEAd-C) with well-defined main-chain lengths, are successfully constructed by a facile method. POEAd-C3-doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5-7.2), while POEAd-C6-DOX can rapidly release drug following gradual swelling at intracellular pH (5.0-6.0). In vitro cytotoxicity shows that POEAd-C3-DOX exhibits more toxic effect on tumor cells than POEAd-C6-DOX at extracellular pH, but POEAd-C6-DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models...
March 29, 2017: Macromolecular Bioscience
Xu Zhou, Xianyan Qin, Tao Gong, Zhi-Rong Zhang, Yao Fu
d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N3 /TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids...
March 27, 2017: Macromolecular Bioscience
Sydney Hollingshead, Charng-Yu Lin, Julie C Liu
Recombinant protein design allows modular protein domains with different functionalities and responsive behaviors to be easily combined. Inclusion of these protein domains can enable recombinant proteins to have complex responses to their environment (e.g., temperature-triggered aggregation followed by enzyme-mediated cleavage for drug delivery or pH-triggered conformational change and self-assembly leading to structural stabilization by adjacent complementary residues). These "smart" behaviors can be tuned by amino acid identity and sequence, chemical modifications, and addition of other components...
March 24, 2017: Macromolecular Bioscience
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