Table Of ContentVol. 9
Frontiers in Nanobiomedical Research
THE WORLD SCIENTIFIC ENCYCLOPEDIA OF
NANOMEDICINE AND BIOENGINEERING II
Bioimplants, Regenerative Medicine, and
Nano-Cancer Diagnosis and Phototherapy
Synthesis and Biomedical Applications
of Graphene Quantum Dots
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Frontiers in Nanobiomedical Research
ISSN: 2251-3965
Series Editors: Martin L. Yarmush (Harvard Medical School, USA)
Donglu Shi (University of Cincinnati, USA)
Published
Vol. 6 Handbook of Immunological Properties of Engineered Nanomaterials
(In 3 Volumes)
edited by Marina A. Dobrovolskaia and Scott E. McNeil
(Leidos Biomedical Research Inc., USA)
Vol. 7 Multiscale Technologies for Cryomedicine: Implementation from Nano
to Macroscale
edited by Xiaoming He (The Ohio State University, USA) and
John C. Bischof (University of Minnesota, USA)
Vol. 8 Bioengineering in Wound Healing: A Systems Approach
edited by Martin L. Yarmush (Rutgers University, USA & Harvard Medical
School, USA) and Alexander Goldberg (Tel Aviv University, Israel)
Vol. 9 The World Scientific Encyclopedia of Nanomedicine and Bioengineering II:
Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and
Phototherapy (A 3-Volume Set)
edited by Donglu Shi (University of Cincinnati, USA),
Maoquan Chu (Tongji University, China) and
Jiang Chang (Chinese Academy of Sciences, China)
Forthcoming titles
Vol. 10 Tissue Engineering and Nano Theranostics
edited by Donglu Shi (University of Cincinnati, USA) and
Qing Liu (Tongji University, China)
Vol. 11 Cancer Therapeutics and Imaging:
Molecular and Cellular Engineering and Nanobiomedicine
edited by Kaushal Rege and Sheba Goklany
(Arizona State University, USA)
The complete list of titles in the series can be found at
http://www.worldscientific.com/series/fnbmr
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THE WORLD SCIENTIFIC
ENCYCLOPEDIA OF NANOMEDICINE
AND BIOENGINEERING II
Bioimplants, Regenerative Medicine, and
Nano-Cancer Diagnosis and Phototherapy
editor-in-chief: Donglu Shi
East Hospital, Tongji University School of Medicine, Shanghai, China
University of Cincinnati, Ohio, USA
Synthesis and Biomedical Applications
of Graphene Quantum Dots
Vol. 9
editor
Frontiers in
Maoquan Chu
Nanobiomedical
Tongji University, China
Research
World Scientific
NEW JERSEY • LONDON • SINGAPORE • BEIJING • SHANGHAI • HONG KONG • TAIPEI • CHENNAI • TOKYO
9559_9789814667647_TP_V1.indd 2 14/7/17 9:13 AM
Published by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE
Library of Congress Cataloging-in-Publication Data
Names: Shi, Donglu, editor.
Title: The World Scientific encyclopedia of nanomedicine and bioengineering. II, Bioimplants, regenerative
medicine, and nano-cancer diagnosis and phototherapy / chief editor, Donglu Shi.
Other titles: Encyclopedia of nanomedicine and bioengineering | Bioimplants, regenerative medicine, and
nano-cancer diagnosis and phototherapy | Frontiers in nanobiomedical research ; v. 9. 2251-3965
Description: New Jersey : World Scientific, 2016. | Series: Frontiers in nanobiomedical research ; volume 9 |
Includes bibliographical references and index.
Identifiers: LCCN 2016040312 | ISBN 9789814667586 (hardcover : alk. paper)
Subjects: | MESH: Biocompatible Materials | Nanostructures | Theranostic Nanomedicine |
Tissue Engineering | Prostheses and Implants | Regeneration
Classification: LCC R856.A3 | NLM QT 37 | DDC 610.2803--dc23
LC record available at https://lccn.loc.gov/2016040312
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Copyright © 2017 by World Scientific Publishing Co. Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or
mechanical, including photocopying, recording or any information storage and retrieval system now known or to
be invented, without written permission from the publisher.
For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center,
Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from
the publisher.
Typeset by Stallion Press
Email: [email protected]
Printed in Singapore
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b2227-P2-V1 Synthesis and Biomedical Applications of Graphene Quantum Dots
Preface
Nanobiomedicine refers to the biomedical applications of natural or synthetic
nanomaterials, biological nanodevices or nanomachines. This is an emerging
scientific discipline which has great potential for imaging, early diagnosis, and
targeted therapy of numerous intractable diseases such as cancer. In nanobio-
medicine research field, nanomaterials may be the most important tools
which have greatly improved the advancement of the biomedical areas. The
biomedical applications of nanomaterials include reducing drug resistance,
improving drug water solubility, targeted drug delivery, and controlled drug
release, in vivo tumor non-invasive imaging and targeted cancer therapy.
The most commonly used nanomaterials for biomedical applications
include graphene-based nanoparticles, magnetic nanoparticles, gold
nanostructures, semiconductor nanoparticles, rare earth doped nanoparticles,
liposomes, polymer micelles, dendrimer-based nanoclusters, etc. Suitable
particle size, morphology and surface zeta potential are important parameters
for these nanoparticles used in biomedical areas. For example, nanoparticles
with small size have the ability of transport through biological barriers and
therefore can deliver the drug to target site. A significant difference between
the tumor and normal tissues is that the tumors exhibit enhanced permeabil-
ity and retention (EPR) effect for macromolecules and nanoparticles. Small
nanoparticles migrating to tumor tissue and finally accumulating in tumor site
after intravenous injection are more easily found than the large nanoparticles.
Therefore, small nanoparticles are usually beneficial for in vivo drug delivery,
targeted imaging and therapy.
In recent years, nanocomposites containing different types of nanoparticles
have been intensively investigated since those hybrids have multifunctional
properties in biomedical applications. However, the great challenge of those
nanohybrids is that the functions of each nanoparticle may be reduced after
the nanoparticles are incorporated into each other. For example, both the
fluorescent intensity and magnetism of a fluorescent colloid/magnetic crystal
v
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b2227-P2-V1 Synthesis and Biomedical Applications of Graphene Quantum Dots
vi Preface
hybrid system are lower than those of the individual nanoparticles, and usually
decrease over time. In addition, the sizes of the hybrids significantly increase
compared with those of the individual nanoparticles. Therefore, one type of
nanoparticle exhibiting multifunctional properties may be more useful than the
single system incorporated with different types of nanoparticles.
Semiconductor quantum dot (QD) is one of the good candidates which
meet the above requirements: small size and multifunctional properties.
These nanocrystals are spherical in shape with only 1–10 nm in diameter.
QDs have attracted great interest in biomedical research fields mostly due to
the excellent optical properties such as size-dependent fluorescence, high
fluorescent quantum yield and long-term photostability. They have been
widely applied for in vitro and in vivo fluorescent labeling and imaging. QDs
are also excellent photodynamic therapy (PDT) and photothermal therapy
(PTT) agents which can significantly inhibit mouse tumor growth under red
or near-infrared (NIR) laser irradiation. However, the components of QDs
are mainly from groups II–VI, III–V, or IV–VI, which are composed of toxic
atoms (e.g. cadmium).
Graphene quantum dot (GQD) is another QD which has similar proper-
ties as the semiconductor QD but has no toxic heavy metal atoms. GQDs are
multifunctional nanomaterials with less than 10 nm in size, which are usually
called zero-dimensional (0D) graphene nanosheets.
Both “top-down” and “bottom-up” techniques have been introduced to
prepare such small nanosheets. For example, large-sized graphene can be
physically cut into pieces through strong acid treatment; small aromatic
molecules after pyrolysis or carbonization can be built into GQDs.
Since GQDs are only several nanometers and have only one or several
layer(s) of carbon atoms, GQDs have huge specific surface areas for loading
drugs. Both the two faces and edge of the GQDs can be loaded with drug
through π–π stacking interaction between the drugs and GQDs and/or
through electrostatic adsorption. Due to the small size, the drug-loaded
GQDs after intravenous injection may conveniently accumulate in tumor
tissue through EPR effect. Therefore, GQDs may be excellent drug delivery
tools. For the semiconductor QDs, however, they cannot be efficiently
loaded with drugs. As for the large-sized graphene nanosheets, they may not
be suitable for intravenous injection compared with the GQDs.
Although GQDs are small-sized graphene nanosheets, some of their
physical properties are different from those of the large-sized graphene. For
example, large graphene sheets are semimetals or specific semiconductors
with zero bandgap energy. However, when the graphene size decreases to less
than 10 nm (has been changed to GQDs), these small graphene sheets have
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b2227-P2-V1 Synthesis and Biomedical Applications of Graphene Quantum Dots
Preface vii
remarkable quantum confinement and edge effects, which have great poten-
tial applications in o ptical and electronic devices. It has been demonstrated
that GQDs have stable fluorescence ranging from blue to red band. Therefore,
GQDs can be used as fluorescent probes for in vitro labeling and in vivo tar-
geted imaging. The fluorescence of most organic fluorescent dyes and semi-
conductor QDs is not stable in physiological environment, whereas GQDs
usually exhibit resistance to photobleaching in vitro and in vivo, which make
them as potential nanoprobes for long-term tracking the intracellular activi-
ties, biodistribution and metabolism of drugs in vivo.
GQDs are not only electron donors but also electron acceptors.
Therefore, resonance energy transfer (RET) usually occurs between the
GQDs and molecules or particles around the GQDs. Chemical sensor and
biosensor of GQDs have been recently developed based on the fluorescence
RET or luminescence RET. These GQD-based sensors have great potential
for medical, pharmaceutical and food detections.
Upon blue or red laser irradiation, GQDs absorb laser light energy and
produce reactive oxygen species (ROS), especially singlet oxygen (1O ).
2
Bacterials can be killed by these ROS produced by the laser-triggered GQDs.
Although GQDs have broad light absorption spectrum, the absorption band
mainly locates ranging from ultraviolet to visible wavelength. GQDs under
NIR laser irradiation may therefore produce little ROS. However, PDT in
clinic has been usually applied for the treatment of superficial tumors such as
skin cancer, nasopharyngeal carcinoma and esophageal cancer, and red laser
has been successfully used for irradiating the photosensitizers in tumors.
Therefore, GQDs may have potential for in vivo cancer PDT.
In addition, GQD aqueous solution with a suitable concentration can
convert laser light energy into heat. This means that GQD is also a
photothermal agent which can be used for cancer PTT. This is an interesting
phenomenon since GQDs are both PDT and PTT agents. The growth of
mouse tumors was significantly inhibited after the tumors were injected with
high-dose GQDs and irradiated with a red (e.g. 671 nm) laser, which may be
due to the synergistic effect of PDT and PTT.
The toxicity of the GQDs to cells and animals may be mainly dependent
on the GQD concentration. Under the same dose, GQDs are safer than other
interesting nanoparticles such as semiconductor QDs and graphene oxide
(GO). For introducing the GQDs into future clinical uses, the in vivo
metabolic pathways and potential toxicity should be further investigated.
In this book, the synthesis strategies and optical properties of the GQDs,
plasmon behavior in GQDs, GQDs for medical and pharmaceutical analysis
as well as food detections, in vitro and in vivo fluorescent imaging, drug
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b2227-P2-V1 Synthesis and Biomedical Applications of Graphene Quantum Dots
viii Preface
delivery and the toxicity of the GQDs to cells and animals were summarized
and discussed. The front line researchers, who are focusing on the research
of graphene-based nanomaterials and nanobiomedicine, were specially
invited by me, and have written six chapters. I also contributed two chapters
and designed the book cover. I would like to take this opportunity to grate-
fully acknowledge all invited authors for their excellent contributions to this
book. I hope this book will provide useful information on the preparation
and properties as well as the biomedical applications of GQDs.
Prof. Maoquan Chu (储茂泉)
Research Center for Translational Medicine at Shanghai East Hospital,
150 Jimo Road, Shanghai 200120, P.R. China
and
School of Life Science and Technology, Tongji University,
1239 Siping Road, Shanghai 200092, P.R. China
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b2227-P2-V1 Synthesis and Biomedical Applications of Graphene Quantum Dots
About the Editor
Professor Maoquan Chu was born in Anhui
Province in China. He received his Ph.D. in
Chemical Engineering from East China University
of Science and Technology in 2001. He then did
his postdoctoral work in the School of Life Science
and Technology in Shanghai Jiaotong University,
where he delved into biomaterials and nanotech-
nology. In 2004, he attended the School of Life
Science and Technology at Tongji University. In
2007, he won the China Education Ministry’s
“New Century Excellent Talents Supporting Plan”.
In 2008, he was hired as a Professor and Ph.D. supervisor. He is now a
principal investigator at the School of Life Science and Technology, Tongji
University and also at the Research Center for Translational Medicine,
Shanghai East Hospital in China. His main area of research is nanobiomedicine,
with a current focus on cancer imaging and therapy using nanobiomaterials.
His recent research work has been published in many important journals such
as Small, Biomaterials, Nanotoxicology, Theranostics, Nanoscale, Carbon, etc.
ix
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