Dendrimers in Biomedical Applications: Rsc - Hardcover

Hardcover

ISBN 10: 1849736111 ISBN 13: 9781849736114

Verlag: ROYAL SOCIETY OF CHEMISTRY, 2013

Inhaltsangabe

Dendrimers are important molecules that are currently undergoing investigation for use in a variety of different biomedical applications. This book explores the use of dendrimers for a variety of potential functions, including antiamyloidogenic agents, drug delivery systems, nucleic acid and RNA delivery vectors and to produce hybrid fibre platforms for nantechnology. Following the work of COST action TD0802, the main objective of which is to improve existing therapies and find new drugs based on dendrimers, the book will provide comprehensive coverage of dendrimer applications. Coverage includes modelling and molecular dynamic studies of dendrimers and dendrons, anionic dendrimer polymers, cationic carbosilane dendrimers and self-assembled multivalent dendrimers. Providing clear indications for future research and applications, this text will appeal to chemists, biologists and materials scientists, working in both academia and industry.

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Dendrimers are important molecules that are currently undergoing investigation for use in a variety of different biomedical applications. This book explores the use of dendrimers for a variety of potential functions, including antiamyloidogenic agents, drug delivery systems, nucleic acid and RNA delivery vectors and to produce hybrid fibre platforms for nantechnology. Following the work of COST action TD0802, the main objective of which is to improve existing therapies and find new drugs based on dendrimers, the book will provide comprehensive coverage of dendrimer applications. Coverage includes modelling and molecular dynamic studies of dendrimers and dendrons, anionic dendrimer polymers, cationic carbosilane dendrimers and self-assembled multivalent dendrimers. Providing clear indications for future research and applications, this text will appeal to chemists, biologists and materials scientists, working in both academia and industry.

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Dendrimers in Biomedical Applications

By Barbara Klajnert, Ling Peng, Valentín Ceña

The Royal Society of Chemistry

Copyright © 2013 COST Office
All rights reserved.

ISBN: 978-1-84973-611-4

Contents

DENDRIMERS AS ANTIAMYLOIDOGENIC AGENTS. DENDRIMER-AMYLOID AGGREGATES MORPHOLOGY AND CELL TOXICITY D. Appelhans, N. Benseny, 0. Klementiveva, M Bryszewska, B. Klajnert, and J. Cladera, 1, 
DENDRIMER-BASED HYBRID FIBERS AS POTENTIAL PLATFORM FOR 1D-OBJECTS IN NANOTECHNOLOGY A. Fahrni, D. Appelhans, A. Danani, G. M Pavan, and B. Voit, 14, 
NATURAL AND SYNTHETIC BIOMATERIALS AS COMPOSITES OF ADVANCED DRUG DELIVERY NANO SYSTEMS (ADDNSS). BIOMEDICAL APPLICATIONS K. Gardikis, E. A. Mourelatou, M Jonov, A. Aserin, D. Libster, B. Klajnert, M Bryszewska, N Garti, J. P. Majoral, K. Dimas, and C. Demetzos, 30, 
CATIONIC CARBOSILANE DENDRIMERS AS NON-VIRAL VECTORS OF NUCLEIC ACIDS (OLIGONUCLEOTIDE OR siRNA) FOR GENE THERAPY PURPOSES R. Gomez, F. J. de la Mata, J. L. Jimenez-Fuentes, P. Ortega, B. Klajnert, E. Pedziwiatr-Werbicka, D. Shcharbin, M Bryszewska, M Maly, J. Maly, M J. Serramia, R. Lorente, and M A. Munoz-Fernandez, 40, 
ANIONIC DENDRITIC POLYMERS FOR BIOMEDICAL APPLICATIONS D. Gröpger, A. Sousa-Herves, M Calderón, E. Fernandez-Megia, and R. Haag, 56, 
POLY(AMIDOAMINE) DENDRIMERS AS NON-VIRAL VECTORS FOR THE DELIVERY OF RNA THERAPEUTICS X Liu, P. Posocco, C. Liu, T Yu, Q. Wang, V Dal Col, C. Chen, Y Wang, P. Rocchi, S. Friel, and L. Peng, 73, 
DENDRIMERIC ANTIGENS. NEW APPROACHES TOWARDS DETECTION OF IgE-MEDIATED DRUG ALLERGY REACTIONS M.I. Montanez, C. Mayorga, M.J. Torres, A.J. Ruiz-Sanchez, M. Malkoch, A. Hult, M. Blanca, and E. Perez-Inestrosa, 84, 
MOLECULAR DYNAMICS OF LYSINE DENDRIMERS. COMPUTER SIMULATION AND NMR I. Neelov, S. Falkovich, D. Markelov, E. Paci, A. Darinskii, and H. Tenhu, 99, 
CHARACTERIZATION OF DENDRIMERS AND THEIR INTERACTIONS WITH BIOMOLECULES FOR MEDICAL USE BY MEANS OF ELECTRON MAGNETIC RESONANCE M. F. Ottaviani, D. Appelhans, F. Javier de la Mata, S. García-Gallego, R. Mazzeo, M. Cangiotti, L. Fiorani, J. P. Majoral, A. M. Caminade, M Bryszewska, and B. Klajnert, 115, 
DENDRIMERS AS VECTORS FOR SMALL INTERFERING RNA TRANSFECTION IN THE NERVOUS SYSTEM F. C. Pérez-Martínez, A. V. Ocaña, G. M. Pavan, A. Danani, and V. Ceña, 134, 
MULTISCALE MODELING OF DENDRIMERS AND DENDRONS FOR DRUG AND NUCLEIC ACID DELIVERY P. Posocco, E. Laurini, V Dal Col, D. Marson, L. Peng, D.K. Smith, B. Klajnert, M. Bryszewska, A.-M. Caminade, J.P. Majoral, M. Fermeglia, K. Karatasos and S. Pricl, 148, 
POLY(AMINOESTER) DENDRIMERS: DESIGN, SYNTHESIS AND CHARACTERIZATION G. Quéléver, C. Bouillon, P. Moreno, A. Tintaru, L. Charles, S. Pricl, and L. Peng, 167, 
FROM MULTIVALENT DENDRONS TO SELF-ASSSEMBLED MULTIVALENT DENDRIMERS: A COMBINED EXPERIMENTAL AND THEORETICAL APPROACH D.K. Smith, and S. Pricl, 179, 
SUBJECT INDEX, 200, 

CHAPTER 1

DENDRIMERS AS ANTIAMYLOIDOGENIC AGENTS. DENDRIMER-AMYLOID AGGREGATES MORPHOLOGY AND CELL TOXICITY

D. Appelhans, N. Bensen, O. Klementiveva, M. Bryszewska, B. Klajnert and J. Cladera K.

1 SUMMARY

Dendrimers are branched polymeric structures that have been shown to have a promising antiamyloidogenic potential by interfering with the polymerization process leading to the formation of the amyloid aggregates related to conformational diseases, such as Alzheimer's and prion diseases. It has been established that there is a relationship between the morphology of the amyloid aggregates and the amyloid peptides or proteins toxicity: fibrillar structures present low or no toxicity, whereas oligomeric species and amorphous aggregates, the so called granular non-fibrillar aggregates (GNAs), are toxic to cells. When interacting with the amyloid peptide associated to the onset and development of Alzheimer's disease, dendrimers can either accelerate the formation of fibrillar structures or inhibit it. Inhibition however may mean promoting the formation of amorphous aggregates. We summarize in the present chapter the experimental evidence showing that when used in a way that favors the formation and clumping of fibrils, dendrimers (glycodendrimers in particular) can reduce amyloid toxicity. However the same glycodendrimers used under different conditions can generate toxic GNAs, an aggregated form that could represent a general morphological signature for amyloid toxicity.

2 AMYLOID AGGREGATION AND ALZHEIMER'S DISEASE.

Alzheimer's disease is one of the so called 'conformational diseases', characterized by the accumulation in the organism of a misfolded variant of a peptide or protein in the form of an amyloid deposit, usually associated to tissue regions where cell deterioration is observed. In Alzheimer's disease, a pathological condition of the Central Nervous System (CNS) which evolution implies the degeneration of cognitive functions, amyloid plaques are typically observed in histological preparations from the affected brains. Such plaques, observed under the electron microscope are made of very thin (approximately 10 nm in diameter) and long (micrometers) amyloid fibrils (Fig. 1A). The main component of amyloid fibrils is the amyloid peptide, a 40-42 residues long peptide (Fig. 1B) which is the proteolytic product of the Amyloid Precursor Protein (APP). APP is a membrane protein which function in the CNS is yet not well established and that can be processed by three different secretases: when cleaved by the α and β secretases a non-amyloidogenic peptide is generated; however when processed by the β and γ secreatases, α mixture of 40 and 42 residues long amyloid peptides, with a high tendency to aggregate is produced into the extracellular space of the CNS.

2.1 Amyloid Peptide Aggregation and Cell Toxicity.

The formation of amyloid fibrils has been thoroughly studied in vitro. The amyloid peptide is structured in the fibril in the form of a cross β-sheet and fibril formation follows a nucleation-dependent polymerization mechanism (Fig. 2). During the lag phase of the typically sigmoid-shaped kinetics different forms of non-fibrillar, low and high molecular weight intermediates are formed. There is a mounting amount of evidence pointing to some of these non-fibrillar species that form during the nucleation phase as the amyloid species that may cause cytotoxicity, whereas mature fibrils would have very low toxicity.

In the search for compounds that would inhibit cell deterioration in Alzheimer's disease, there is a marked interest in finding compounds which are able to inhibit the formation of amyloid deposits either by promoting the removal of the amyloid peptide from the CNS or by inhibiting the formation of the toxic amyloid species or blocking their action. Given the non-toxic character of amyloid fibrils it has to be considered that one way of avoiding the amyloid peptide toxicity could be via its rapid association into fibrils.

Many studies can be found in the literature dedicated to study the effects of a very diverse number of compounds on the amyloid peptide aggregation kinetics. In many cases, it is considered that the power of a compound to inhibit fibril formation represents the possibility that such a compound could be useful to inhibit the peptide's cell toxicity.

However, when evaluating the results of such studies, one has to consider t he possibility that the fact of inhibiting the formation of fibrils, may implicate the accumulation of non-fibrillar toxic species, high and low molecular weight...

Details zur Ausgabe

• Verlag: ROYAL SOCIETY OF CHEMISTRY
• Erscheinungsdatum: 2013
• Sprache: Englisch
• ISBN 10: 1849736111
• ISBN 13: 9781849736114
• Einband: Gebundene Ausgabe
• Auflage: 1
• Anzahl der Seiten: 204
• Herausgeber: Klajnert Barbara, Peng Ling, Cena Valentin
• Kontakt zum Hersteller: Nicht verfügbar
• Verantwortliche Person: Nicht verfügbar