Download Biomedicine - C. Lin (Intech, 2012) WW PDF

TitleBiomedicine - C. Lin (Intech, 2012) WW
TagsMedical
LanguageEnglish
File Size11.8 MB
Total Pages212
Table of Contents
                            00 preface_ Biomedicine
Part 1_ Regenerative Medicine
01_ Encapsulation and Surface Engineering of
Pancreatic Islets: Advances and Challenges
02_ In-Situ Forming Biomimetic Hydrogels
for Tissue Regeneration
Part 2_ Gene Medicine and Nanobiomedicine
03_ RNA Interference for Tumor Therapy
04_ Bioreducible Cationic Polymers
for Gene Transfection
05_ Stable Magnetic Isotopes as a
New Trend in Biomedicine
Part 3_ Medical Device Performance
06_ Optical Fiber Gratings in Perspective
of Their Applications in Biomedicine
07_ Additive Manufacturing Solutions
for Improved Medical Implants
Part 4_ Public Perception of Biomedicine
08_ Crossings on Public Perception of Biomedicine:
Spain and the European Indicators
                        
Document Text Contents
Page 1

BIOMEDICINE


Edited by Chao Lin

Page 2

Biomedicine
Edited by Chao Lin


Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2012 InTech
All chapters are Open Access distributed under the Creative Commons Attribution 3.0
license, which allows users to download, copy and build upon published articles even for
commercial purposes, as long as the author and publisher are properly credited, which
ensures maximum dissemination and a wider impact of our publications. After this work
has been published by InTech, authors have the right to republish it, in whole or part, in
any publication of which they are the author, and to make other personal use of the
work. Any republication, referencing or personal use of the work must explicitly identify
the original source.

As for readers, this license allows users to download, copy and build upon published
chapters even for commercial purposes, as long as the author and publisher are properly
credited, which ensures maximum dissemination and a wider impact of our publications.

Notice
Statements and opinions expressed in the chapters are these of the individual contributors
and not necessarily those of the editors or publisher. No responsibility is accepted for the
accuracy of information contained in the published chapters. The publisher assumes no
responsibility for any damage or injury to persons or property arising out of the use of any
materials, instructions, methods or ideas contained in the book.

Publishing Process Manager Anja Filipovic
Technical Editor Teodora Smiljanic
Cover Designer InTech Design Team

First published March, 2012
Printed in Croatia

A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]


Biomedicine, Edited by Chao Lin
p. cm.
ISBN 978-953-51-0352-3

Page 106

Biomedicine



94

blood plasma (intracellular vs. extracellular glutathione concentration, 0.5-10 mM vs. 2-20
μM) (G. Wu et al., 2004). Thus, this feature makes the disulfide very valuable in the design
of biodegradable cationic polymers for triggered gene delivery. Figure 4 shows a schematic
illustration on intracellular gene delivery mediated by disulfide-based cationic polymers.

+

HS

SH

HS

SH

SH

SH

self
assembly

disulfide
cleavage

DNA
release

SH

SH


Fig. 4. A conceptual illustration of DNA binding and subsequent intracellular release: (a)
formation of the polyplexes of bioreducible cationic polymers, which are relatively stable in
the extracellular environment, (b) intracellular cleavage of disulfide linkages in the polymer
of the polyplex, and (c) intracellular DNA release from the degraded polymer.

This section reviews current progress in disulfide-based cationic polymers as non-viral gene
delivery vectors. The topics are focused on the synthesis of bioreducible cationic polymers,
unique biophysical properties of the polyplexes based on the polymers.

5.1 Preparation of bioreducible cationic polymers as non-viral gene vectors

Bioreducible cationic polymers can be designed and synthesized that contain disulfide bond
either in polymer main chain or side chain. In earlier studies, the disulfide was introduced in
the polymer side chain to conceptually confirm the role of the disulfide in gene delivery. A
typical synthesis route is the preparation of cationic polymers with pyridyldithio residue, which
is then modified with suitable thiol compounds via an exchange reaction (Figure 5a). By this
method, the pLL containing disulfide linkages in the polymer side chains (termed as poly[Lys-
(AEDTP)]) was prepared through chemical modification of the primary amines in pLL with N-
succinimidyl-3-(2-pyridyldithio)propionate, followed by an exchange reaction with
mercapthoethylamine (Pichon et al., 2002). The polyplexes of poly[Lys-(AEDTP)] can transfect
HeLa cells with a level of gene expression 10-fold higher than that of parent pLL. This thus
implies that disulfide linker plays a pivotal role in improved gene transfection. In another work,
PAEs with pyridyldithio groups in the polymer side chains were synthesized via Michael-type
addition reaction between diacrylates and 2-(pyridyldithio)-ethylamine. These polymers were
further modified with mercaptoethylamine or thiol peptide such as RGD, yielding the PAEs
with disulfide linkers in the side chains (SS-PAEs) (Zugates et al., 2006). The polyplexes of SS-
PAEs could transfect HCC cells with the efficiency comparable to that of 25-kDa PEI.

Page 107

Bioreducible Cationic Polymers for Gene Transfection



95

N
H

S
O

S N
H

O
N
H

S
O

S N
H

O

N *
*

R
n

b)

+
NH2
R

O S S
O

O

O
N

N
O

O

O

O
+ PEI N

H
S S

O H
N

O
PEI

PEI

O S S
NH2+ Cl-

O

NH2+ Cl-
+ PEI N

H
S S

NH2+ Cl- H
N

NH2+ Cl-
PEI

PEI

CBA

c)

DTSP

a)
S
S

N
+

HS

R
+

S

HN

HS SH S S **

d)

e)

DTBP

S
S

R

polymer main chain polymer main chain


Fig. 5. Typical methods for the preparation of bioreducible cationic polymers as non-viral
gene delivery vectors

Alternatively, one route to generate bioreducible cationic polymers is the polyoxidation of
dithiol-based monomers having amino groups (Figure 5b). Typical examples are disulfide-
containing cationic polymers based on pEI , pLL and pDMAEMA (SS-PEI, SS-PLL and SS-
PDMAEMA, respectively, in Figure 5). In general, the preparation of these dithiol-based
oligoamines is time-consuming and these compounds can not be stored for long term due to
oxidation of thiol groups by air. As typical examples, Park et al. reported on the synthesis of
dithiol-containing oligoamines via organic synthesis involving protection and deprotection
of amino groups (Lee et al., 2007). Oupický et al. described the preparation of well-defined
dithiol-based PDMAEMA oligomers via reversible addition-fragmentation chain transfer
polymerization (You et al., 2007). Seymour et al. produced dithiol-based oligopeptides (Cys-
Lys10-Cys) via solid-phase organic synthesis (Oupicky et al., 2002). These dithiol-based
oligoamines can be oxidized by DMSO as an oxidant agent to yield disulfide-containing
cationic polymers. Also, different dithiol-bearing groups, e.g. nuclear localization sequences
comprising two cysteine residues, can be incorporated in the oxidation reaction, giving rise
to disulfide-containing copolymers with multiple functionalities (Read et al., 2005).

A simple approach for the availability of disulfide-based cationic polymers is the chemical
coupling of amine compounds with disulfide-containing reagents, such as cystamine
bisacrylamide (CBA) in a Michael addition reaction (Lin et al., 2006, 2007a; Lin et al., 2007b;
Lin et al., 2008; Lin & Engbersen, 2008) (Figure 5c), and dithiobis(succinimidyl propionate)
(DTSP) or dithiobispropionimidate (DTBP) in a polycondensation reaction (Figures 5d&e).
These reactions can generate linear or branched disulfide-containing cationic polymers with
different molecular structures (Figure 6). Lee et al. firstly prepared disulfide-containing
branched pEI by the crosslinking of low molecular weight PEI with DTSP or DTBP (Gosselin

Page 211

Crossings on Public Perception of Biomedicine: Spain and the European Indicators



199

mechanisms to favor greater public participation in the regulation and risk prevention of
them.

5. Acknowledgment
This chapter was carried out as part of the Cartographies of Science and Technology:
Ethnographies, Images and Epistemologies (FFI 2009-07138-FISO) project.

6. References
Atienza, J. Luján, J.L. (1997), La Imagen Social de las Nuevas Tecnologías Biológicas en España,

CIS: Madrid (The Social Image of New Biological Technologies in Spain)
Bauer, M. W., (2009), “The evolution of public understanding of science-Discourse and

comparative evidence”, Science, Technology & Society, 14: 221 – 242
Bauer, M. W., (2003), “Controversial medical and agri-food biotechnology: a cultivation

analysis”, Public Understanding of Science, 11: 93 – 113
Bauer, M., y Schoon, I., (1993), “Mapping Variety in Public Understanding of Science” Public

Understanding of Science, 2 (1993): 141–155
European Commission, (1991), Eurobarometer 35.1. Commission of the European

Communities: Brussels
European Commission, (1993), Eurobarometer 38.1. Europeans, Science and Technology: Public

Understanding and/ Attitudes, Commission of the European Communities: Brussels
European Commission, (1996), Eurobarometer 46.1. Commision of the European

Communities: Brussels
European Commission, (2002), Eurobarometer 58.0. Europeans and Biotechnology in 2002,

European Commission.
European Commision, (2005a), Eurobarometer 64.3. Europeans and Biotechnology in 2005:

Patterns and Trends, European Commission: Luxembourg
European Commission, (2005b), Europeans, Science and Technology, European Commission:

Luxembourg
European Commission, (2010a), Europeans and Biotechnology in 2010. Winds of change?,

European Commission: Luxembourg
European Commission, (2010b), Science and Technology, European Commission: Luxembourg
FECYT (2006): Tercera encuesta nacional sobre percepción social de la ciencia, Madrid.
FECYT (2010): Quinta encuesta nacional sobre percepción social de la ciencia, Madrid.
Fundación BBVA, (2008), “Actitudes hacia la investigación con células madre”, II Estudio de

Biotecnología de la Fundación BBVA (“Attitudes Toward Stem Cell Research”, II
Study of Biotechnology from the BBVA Foundation)

IESA, (1990) Biotecnología y Opinión Pública en España, Instituto de Estudios Sociales
Avanzados: Madrid (Biotechnology and Public Opinion in Spain, Institute of
Advanced Social Studies: Madrid)

Luján, J. L. y Todt, O., (2000), “Perceptions, attitudes and ethical valuations: the ambivalence
of the public image of biotechnology in Spain”, Public Understanding of Science, 9:
383-392

Marlier, E., (1991), “Eurobarometer 35.1: Opinions of Europeans on Biotechnology”in
Biotechnology in Public

Page 212

Biomedicine



200

Moreno, L., (1996), “La Opinión Pública y los Avances en Genética,” in ed. Borrillo, D., Genes
en el Estrado, CSIC: Madrid (“Public Opinion and Genetic Advances”)

Pérez Sedeño, E. And Miranda Suárez, M.J. (2008): “Percepción pública de la biomedicina en
España”, Medicina Clínica, : 131 (Sup. 3) : 6-12 (“Public Perception of Biomedicine in
Spain,” Clinical Medicine, : 131 Sup.3)

Todt, O., Muñoz, E., González, M., Ponce, G., Estévez, B., (2009), “Consumer attitudes and
the governance of food safety”, Public Understanding of Science, 18: 103-116

Similer Documents