Nanotechnology for the Delivery of Therapeutic Nucleic Acids

232 Pages·2013·8.83 MB·English

by  Dan Peer

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MCaicnrocedre Lveictteesr, s .and Cancer Letters.
Dan PDeaenr Peer
EditorEditor
V335
ISBN 978-981-4411-04-2
9-78981-4411042
Nanotechnology
for the Delivery of
Therapeutic Nucleic Acids
Pan Stanford Series on Biomedical Nanotechnology
Series Editors
Vladimir Torchilin and Monsoor Amiji
Titles in the Series
Vol. 1 Vol. 5
Handbook of Materials Inorganic Nanomedicine
for Nanomedicine
Bhupinder Singh Sekhon, ed.
Vladimir Torchilin and Monsoor Amiji, 2014
eds. 2010
978-981-4267-55-7 (Hardcover) Vol. 6
978-981-4267-58-8 (eBook)
Nanotechnology for Cancer
Vol. 2 Julia Ljubimova, ed.
2014
Nanoimaging
Beth A. Goins and William T. Phillips,
Vol. 7
eds. 2011
Nanotechnology for Delivery of
978-981-4267-09-0 (Hardcover)
DNA and Related Materials
978-981-4267-91-5 (eBook)
Bengt Fadeel, ed.
Vol. 3 2015
Biomedical Nanosensors
Vol. 8
Joseph Irudayraj, ed.
2013 Translation Industrial
Nanotechnology
978-981-4303-03-3 (Hardcover)
978-981-4303-04-0 (eBook) Thomas Redelmeier, ed.
2015
Vol. 4
Nanotechnology for the Delivery
of Therapeutic Nucleic Acids
Dan Peer, ed.
2013
978-981-4411-04-2 (Hardcover)
978-981-4411-05-9 (eBook)
Nanotechnology
for the Delivery of
Therapeutic Nucleic Acids
Dan Peer
Editor
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2013 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
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Version Date: 20130418
International Standard Book Number-13: 978-981-4411-05-9 (eBook - PDF)
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Contents
Preface
xi
1. Lipoplexes and Polyplexes: From Gene Delivery to
Gene Expression 1
Gerardo Byk, Mirit Cohen-Ohana, and Fiana Mirkin
1.1 Introduction 1
1.2 Lipopolyamines 4
1.3 Lipopolyamine Co-formulation with DNA
Complexing Peptides 9
1.4 Lipopolyaminoguanidines 10
1.4.1 Biodegradable Lipoplexes: Reduction-Sensitive
Lipopolyamines 12
1.4.2 Biodegradable Polyplexes: Reduction-Sensitive
Dendrimers 15
1.5 Towards Non-Electrostatic DNA Complexing
Agents 18
1.6 Site-Specific Chemical Ligation of Targeting
Peptides to Plasmid DNA 20
2. C1a.7ti onCico nPcolluydminergs Rfoerm tahrek Ds ealnivde Fryu touf rTeh Deriraepcetuiotincs 20
Nucleotides 27
Wahid Khan, Saravanan Muthupandian, and Abraham J. Domb

2.1 Introduction 28
2.2 Cationic Polymer Targeted Delivery of Nucleotides 29
2.3 Major Cationic Polymers Used for Delivery of
Nucleotides 31
2.3.1 Polyethylenimine 31
2.3.2 Poly(L-lysine) 35
2.3.3 Cationic Polysaccharides 37
vi Contents
2.3.3.1 Chitosan 38
2.3.3.2 Cyclodextrins 39
2.3.3.3 Dextran, dextran-spermine 40
2.3.4 Dendrimers 41
2.3.5 Other Cationic Polymers 42
2.3.5.1 Cationic polyesters 42
2.3.5.2 Poly(amino ester)s 44
2.3.5.3 Poly(amido amine)s 45
2.4 Factors Influencing Cationic Polymer Mediated
Nucleotides Delivery 46
2.5 Biomedical Applications 47
2.5.1 Tumor Therapy 47
2.5.2 siRNA Delivery 48
2.5.3 DNA Vaccination 49
2.5.4 Lung and Liver Delivery 49
2.5.5 Brain Delivery 50
3. M2.e6m bCroanncel/uCsoioren Nanoparticles for Delivery of Therapeutic 50
Nucleic Acid 57
Younjee Chung and Leaf Huang
3.1 Introduction 58
3.2 Challenges in Nanocarrier Systems 60
3.3 Current Non-Viral Carrier Systems 62
3.4 Membrane/Core NPs 65
3.4.1 LPD 67
3.4.1.1 Formulation of LPD 67
3.4.1.2 The effect of surface modification
of LPD 69
3.4.1.3 Therapeutic applications of LPD 71
3.4.1.4 Modified LPD formulations 73
3.4.2 LCP 76
3.4.2.1 Physicochemical characteristic
of LCP 78
3.4.2.2 Potential therapeutic effect of LCP 78
3.5 Conclusion 80
Contents vii
4. Delivery of Single siRNA Molecules 93
Caroline Palm-Apergi and Steven F. Dowdy
4.1 Introduction 94
4.1.1 RNA Interference 94
4.1.2 Modification of siRNAs 95
4.1.3 Off-Target Effects 96
4.2 Delivery of siRNA 96
4.2.1 Peptide Transduction Domains 96
4.2.2 Delivery of siRNA-PTD Nanoparticles 97
4.2.3 RNA Binding Proteins 98
4.2.4 Delivery of Single siRNA Molecules by
PTD-DRBD 99
4.3 Discussion 100
5. C4e.4ll -SpCeocnifcilcu Asipotnasm er-Functionalized RNAi: A New 102
Prospect for Targeted siRNA Delivery 107
Jiehua Zhou and John J. Rossi
5.1 Introduction 108
5.2 Generation of Cell-Specific Aptamers 111
5.2.1 Recombinant Protein-Based SELEX
Procedure 111
5.2.2 Whole Cell-Based SELEX Procedure 112
5.3 Cell-Specific Aptamer-Functionalized RNAi 114
5.3.1 Cell-Specific Aptamer-Functionalized
siRNAs 115
5.3.1.1 PSMA RNA aptamer-functionalized
siRNAs 115
5.3.1.2 HIV gp120 RNA aptamer-
functionalized siRNAs 116
5.3.1.3 CD4 RNA aptamer-functionalized
siRNAs 117
5.3.2 Cell-Specific Aptamer-Functionalized
Therapeutic Nanocarriers 117
5.3.2.1 CD4 RNA aptamer-functionalized
pRNA-nanoparticles 118
viii Contents
5.3.2.2 PSMA RNA aptamer-functionalized
polymer nanocarriers 118
5.3.2.3 CD30 RNA aptamer-functionalized
polymer nanocarriers 119
6. B5i.o4r esCpoonncsliuvesi oNnasn oanpadr Ptiecrlessp efocrt itvhees Intracellular 119
Delivery of RNAi Therapeutics 129
Kenneth Alan Howard
6.1 Introduction 129
6.2 Repertoire of Potential RNAi Therapeutics 130
6.3 Nanoparticle-Based Delivery of RNAi Therapeutics 132
6.3.1 Polycation-Based Nanoparticles 132
6.3.2 Bioresponsive Systems 133
6.4 Copolypeptide System 134
6.5 Hyperbranched System 140
7. L6ip.6id -LCioken cDluelsiivoenry Materials for Efficient siRNA 144
Delivery 153
James Dahlman, Robert Langer, and Michael Goldberg
in vivo
7.1 Introduction 154
7.2 Motivation: Need for Novel siRNA Carriers 155
7.3 Approach: Efficient Chemistry Allows for High-
Throughput Combinatorial Library Synthesis
in vitro in vivo
and Screening 155
7.4 Translation: Moving from to
Screening 158
7.5 Optimization: Formulation Parameters Greatly
Influence Carrier Efficacy 160
7.6 Synergy: Combining Existing Compounds to
Achieve Improved Delivery 161
7.7 Next-Generation: Identifying Improved Carriers
Using Innovative Chemistry 162
7.8 Applications: Using Lipidoids to Treat Disease
Models 166
7.9 Future Directions and Conclusions 170
Contents ix
8. Manipulation of Leukocytes Using Therapeutic RNAi
Delivered by Targeted and Stabilized Nanoparticles 179
Dan Peer
8.1 Introduction 180
8.2 Strategies for RNAi Delivery into Leukocytes 182
8.3 CpG-Conjugated siRNA 184
8.4 Atelocollagen-Complexed siRNA 184
8.5 Cationic Nona-d-Arginine Peptide-Complexed
siRNA 185
8.6 I-tsNP as RNAi Delivery Vehicle for Leukocyte-
Associated Diseases 185
8.7 Leukocyte Integrins as Targets for siRNA Delivery 186
In vivo
8.8 The Construction and Characterization of I-tsNP 186
8.9 Gene Silencing Using I-tsNP-Entrapping
siRNAs 187
9. 8L.1o0w erCinogn tchlues sioiRnN A Delivery Barrier: Alginate Scaffolds 188
and Immune Stimulation 193
Jana McCaskill, Sherry Wu, Norliana Khairuddin, and
Nigel A. J. McMillan
9.1 Introduction 193
9.2 siRNA Delivery Systems: A Brief Overview 194
9.2.1 siRNA Conjugate Delivery 194
9.2.2 Peptide-Based Delivery Particles 195
9.2.3 Polymer-Based Delivery Vectors 196
9.2.4 Lipid-Based Delivery Particles 197
in vivo
9.3 HDFM: A Novel Method for Formulating Stable
siRNA-Loaded Lipid Particles for Use 198
9.4 The Challenge of the Vaginal Tract 200
9.5 Vaginal Delivery of siRNA Using a Novel PEGylated
Lipoplex-Entrapped Alginate Scaffold System 202
9.6 Thinking Outside the Box: Bi-Functional siRNAs 205
in vivo
9.7 siRNA-Induced Immunostimulation Promotes
Anti-tumoural Activity 208
Index
9.8 Conclusion 210
217