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Carbon Nanotubes in Drug andGene Delivery

Carbon Nanotubes in Drug andGene Delivery

Mahdi Karimi*Cellular and Molecular Research Center, Iran University of Medical Sciences,

Tehran, IranDepartment of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine,

Iran University of Medical Sciences, Tehran, IranResearch Center for Science and Technology in Medicine, Tehran University of Medical

Sciences, Tehran, IranWellman Center for Photomedicine, Massachusetts General Hospital,

Harvard Medical School, Boston, MA 02114, USA

Amir Ghasemi*Department of Materials Science and Engineering, Sharif University of Technology,

PO Box 11365-9466, 14588 Tehran, IranAdvanced Nanobiotechnology & Nanomedicine Research Group (ANNRG), Faculty ofAdvanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, IranBio-Nano-Interfaces: Convergence of Sciences (BNICS), Universal Scientific Education

and Research Network (USERN), Tehran, Iran

Soroush MirkianiBioceramics and Implants Laboratory, Faculty of New Sciences and Technologies,

University of Tehran, Tehran 1439955941, Iran

Seyed Masoud Moosavi BasriBio-Nano-Interfaces: Convergence of Sciences (BNICS) Group, Universal Scientific

Education and Research Network (USERN), Tehran, IranBioenvironmental Research Center, Sharif University of Technology, Tehran, Iran

Civil & Environmental Engineering Department, Shahid Beheshti University, Tehran, Iran

Michael R HamblinWellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical

School, Boston, MA 02114, USADepartment of Dermatology, Harvard Medical School, Boston, MA 02115, USAHarvard-MIT Division of Health Sciences and Technology, Cambridge, USA

Morgan & Claypool Publishers

*These two authors contributed equally to this book.

Copyright ª 2017 Morgan & Claypool Publishers

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ISBN 978-1-6817-4261-8 (ebook)ISBN 978-1-6817-4262-5 (print)ISBN 978-1-6817-4263-2 (mobi)

DOI 10.1088/978-1-6817-4261-8

Version: 20171001

IOP Concise PhysicsISSN 2053-2571 (online)ISSN 2054-7307 (print)

A Morgan & Claypool publication as part of IOP Concise PhysicsPublished by Morgan & Claypool Publishers, 1210 Fifth Avenue, Suite 250, San Rafael, CA,94901, USA

IOP Publishing, Temple Circus, Temple Way, Bristol BS1 6HG, UK

Dedicated to our beloved parents, and wivesfor their sacrifice through the years.

Contents

Preface x

Acknowledgments xi

Author biographies xii

1 Introduction 1-1

1.1 Introduction 1-1

References 1-3

2 Carbon nanotubes: properties and classification 2-1

2.1 Introduction 2-1

2.2 Classification of CNTs 2-2

2.2.1 Single-walled carbon nanotubes (SWCNTs) 2-3

2.2.2 Double-walled carbon nanotubes (DWCNTs) 2-5

2.2.3 Triple-walled carbon nanotubes (TWCNTs) 2-5

2.2.4 Multi-walled carbon nanotubes (MWCNTs) 2-5

References 2-6

3 Carbon nanotube synthesis and purification 3-1

3.1 Introduction 3-1

3.2 Arc discharge 3-1

3.3 Laser ablation 3-4

3.4 Chemical vapor deposition 3-5

3.4.1 Hot filament CVD 3-5

3.4.2 Plasma-enhanced CVD 3-7

3.4.3 Radio frequency PECVD 3-7

3.4.4 Microwave PECVD 3-8

3.4.5 Water-assisted CVD 3-8

3.4.6 Oxygen-/carbon dioxide-assisted CVD 3-9

3.4.7 CVD with organometallic precursors 3-9

3.5 Purification of CNTs 3-9

References 3-10

4 Carbon nanotube functionalization 4-1

4.1 Introduction 4-1

4.2 Non-covalent attachment 4-1

vii

4.2.1 Surfactants 4-2

4.2.2 Biomolecules 4-3

4.2.3 Polymers 4-7

4.2.4 Peptides 4-8

4.3 Covalent functionalization 4-9

References 4-11

5 Mechanism of carbon nanotube uptake by cells 5-1

5.1 Introduction 5-1

5.2 Energy-dependent and energy-independent uptake and the role ofthe cells

5-2

5.3 Role of lysosomes in CNT cell uptake 5-4

5.4 CNTs in the blood stream 5-4

References 5-5

6 Carbon nanotubes in drug delivery 6-1

6.1 Introduction 6-1

6.2 Cellular uptake mechanisms of CNTs 6-1

6.3 Drug delivery 6-2

6.3.1 Cisplatin 6-4

6.3.2 Doxorubicin 6-4

6.3.3 Other drugs 6-5

References 6-9

7 Carbon nanotubes in gene delivery 7-1

7.1 Introduction 7-1

7.2 Surface functionalization of CNTs for GDSs 7-2

7.3 Gene delivery systems (GDSs) 7-3

7.3.1 Plasmid DNA (pDNA) 7-3

7.3.2 Small-interfering RNA (siRNA) 7-4

7.3.3 Micro-RNA (miRNA) 7-6

References 7-7

8 Toxicity and environmental aspects of carbon nanotubes 8-1

8.1 Introduction 8-1

8.2 Environmental effects of CNTs 8-1

8.3 Effect of the diameter and length of CNTs 8-3

Carbon Nanotubes in Drug and Gene Delivery

viii

8.4 Effect of the type of CNT 8-4

8.5 Effect of impurities present in CNTs 8-4

8.6 Effect of CNT aggregation 8-5

8.7 Effect of CNT functionalization 8-5

8.8 Effect of CNT surface chemistry 8-6

8.9 Effect of CNT dispersion method 8-6

References 8-6

9 Future of carbon nanotubes in medicine 9-1

9.1 Introduction 9-1

Carbon Nanotubes in Drug and Gene Delivery

ix

Preface

Nanotechnology is fast becoming one of the signature scientific fields of the 21stCentury. Ever since Richard Feynman’s famous lecture ‘There’s Plenty of Room atthe Bottom’ delivered in 1959, nanotechnology has steadily and progressively seizedthe imagination of the scientific community, and indeed the general public at large.Feynman proposed that the ability to manipulate matter on an atomic scale couldlead to the construction of ‘nanoscale machines that arrange the atoms the way wewant’. He also presented the possibility of ‘swallowing the doctor’, and perhaps tinysurgical robots could be constructed that could travel throughout the body detectingthe early signs of disease and fixing them before the patient even noticed anysymptoms.

Almost sixty years later it is interesting to see howmuch nanotechnology has reallychanged our lives. There have been large changes in materials science, in nano-electronics, and even consumer products (cosmetics, packaging etc). But how closeare we to realizing the long-held dreams of nanomedicine? Among the manyachievements of nanotechnology (gold nanostructures, quantum dots, fullerenes,mesoporous silica nanoparticles, smart liposomes, etc) carbon nanotubes (CNTs)occupy an almost starring role. Their astonishing properties in terms of mechanicalstrength, ability to conduct both heat and electricity, stability against chemical andphysical degradation, large surface area, tunable aspect ratio, have led to scientistsdevising ever more ingenious applications. But will they have a role in nanomedicine?

The present ebook seeks to provide some answers to this intriguing question.Many medical applications in nanomedcine have centered around the use ofnanovehicles for drug and gene delivery. Smart and targeted drug delivery continuesto fascinate multi-disciplinary nanomedicine laboratories. CNTs are no exception tothis rule of thumb. However, there are concerns about whether CNTs can ever beused in clinical applications, considering widespread fears about possible toxicityand side-effects, even going as far as possible carcinogenicity. In the followingchapters we summarize the properties and synthesis methods of CNTs. We discusstheir interactions with cells, and applications to drug and gene delivery includingsmart stimulus-responsive and targeted approaches. Finally, issues of toxicity andenvironmental damage are addressed.

x

Acknowledgments

We would like to express our special thanks of gratitude to all those who providedsupport during the process of writing and preparing of this book, in particular, toMr Hamed Mirshekari for the process of selection and editing. The authors deeplyextend their appreciation to the guidance and contribution of the Production team atMorgan & Claypool and IOP Publishing, for their expert help.

xi

Author biographies

Mahdi Karimi

Mahdi Karimi received his BSc degree in medical laboratory sciencefrom the Iran University of Medical Science (IUMS), in 2005. In2008, he achieved an MSc degree in medical biotechnology fromTabriz University of Medical Science and joined Tarbiat ModaresUniversity as a PhD student in the nanobiotechnology field, andcompleted his research in 2013.

During his research, in 2012, he became affiliated with thelaboratory of Professor Michael Hamblin in the Wellman Center for Photomedicineat Massachusetts General Hospital and Harvard Medical School as a researchervisitor. There, he contributed to the design and construction of new smartnanoparticles for drug/gene delivery. On finishing his studies, he joined theDepartment of Medical Nanotechnology at IUMS as an assistant professor. Hiscurrent research interests include smart nanoparticle design in drug/gene deliveryand microfluidic systems. He has established a scientific collaboration betweenhis lab and Professor Michael Hamblin’s lab to design new classes of smartnanovehicles in drug/gene delivery systems.

Amir Ghasemi

Amir gained his BSc at Sharif University of Technology (SUT), themost prestigious technical university in Iran. He has been a memberof a polymeric materials research group since 2012, and received hisMSc in materials engineering from SUT. For his MSc project, heworked on thermoplastic starch (TPS)/cellulose nanofibers (CNF)biocomposites, under the supervision of Professor Bagheri. Hesynthesized a fully biodegradable nanocomposite, and evaluated the

effects of CNF on the mechanical- and bio-degradation of TPS. The advent ofinnovative nanomaterials and nanotechnology interested him in interfacial sciences/technologies and also nanomedicine, including nanoparticlebased drug deliverysystems and nanobiosensors. He has now joined Professor Karimi’sNanobiotechnology Research lab in the Iran University of Medical Science, Tehran,Iran, in association with Professor Hamblin from Harvard Medical School, Boston,USA; working on smart micro/nanocarriers applied in therapeutic agent deliverysystems employed for diagnosis and therapy of various diseases and disorders suchas cancers and malignancies, inflammations, infections, etc.

xii

Soroush Mirkiani

Soroush Mirkiani received his BSc from Sharif University ofTechnology at Materials Science and Engineering. He continued hisstudies in the field of Biomaterials at Faculty of New Sciences andTechnology at University of Tehran. During his MSc he developeda degradable Brushite Bone Cement reinforced by calcium phos-phate whiskers. In 2015, he contributed to the AdvancedNanobiotechnology & Nanomedicine Research Group (ANNRG)

at Iran University of Medical Science, starting his researches about smart drugdelivery systems.

Seyed Masoud Moosavi Basri

S M Moosavi-Basri is a young multidisciplinary researcher. Hesucceeds to obtain the Top Student Award in Civil Engineeringdepartment in his BSc. As an engineer with enthusiasm for applyingfundamental science in biology, he conducted his Master thesis InBiomimetics and Bioinspiration at Shahid Beheshti University incollaboration with Bioenvironmental Research Center at SharifUniversity of Technology. He is developing a novel approach

leading to obtaining promising results in Biomimetics. Also, he is pursuing hisinterests in Biology disciplines by holding remote collaborations with some labs andjournals around the globe (e.g. Harvard Medical School, Wyss Institute forBiologically Inspired Engineering, USERN, Iran Pasteur Institute, etc) as aResearcher and Scientific Illustrator as well.

Michael R Hamblin

Michael R Hamblin PhD is a principal investigator at the WellmanCenter for Photomedicine, Massachusetts General Hospital, anassociate professor of dermatology, Harvard Medical School andthe affiliated faculty of Harvard–MIT Division of Health Scienceand Technology. He received his PhD in organic chemistry fromTrent University in the UK. He directs a laboratory of around adozen scientists who work in photodynamic therapy (PDT) and

photobiomodulation. He has published 376 peer-reviewed articles, is Editor orAssociate Editor for ten journals, and serves on NIH study sections. He has anh-factor of 82 and >25 000 citations. He has authored/edited 11 proceedingsvolumes together with ten other major textbooks on PDT and photomedicine.Dr Hamblin was honored by election as a Fellow of SPIE in 2011, and receivedthe 1st Endre Mester Lifetime Achievement Award in Photomedicine from NAALTin 2017.

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