Nanomachines Changing
Cancer Treatment
Contents
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Top Message

Nanomachines which support“In-Body Hospital” is being developed tosupport a Smart Life Care Society
Kazunori KATAOKA

Talking about Theme 1

To Design the Next Anticancer
Drug-Encapsulating Polymeric Micelle
Kanjiro MIYATA, Tetsuya HAMAGUCHI, Kenichiro NAITO

Research Highlights

Success in Developing a Nanomachine to
Pinpoint Cancer Stem Cells
Hiroaki KINOH, Horacio CABRAL

Discovery of a New Tumor Blood Vessel
Permeation Pathway to Increase
the Eﬃcacy of DDS in Cancer!
Yu MATSUMOTO

12 Listen to COINS' Member
What we treasure

Yuki MOCHIDA, Sabina QUADER, Masaru UENO, Tsukasa CHIDA

14 Activity Report

・6th General Meeting
・Topics

Top
S p eMessage
cialInterview

Nanomachines which support“In-Body Hospital” is being
developed to support
a Smart Life Care Society
It has been 3 years since The Ministry of Education, Culture, Sports,
Science and Technology s Radical Innovation and Entrepreneurship
Program（COI STREAM） adopted COINS（Center of Open Innovation
Network for Smart Health）started research based in Kawasaki Instituteof Industrial Promotion Innovation Center of NanoMedicine（iCONM）.
Here are about the COINS concept, mission and current progress fromCOINS s research leader Kazunori Kataoka（concurrently iCONM, Director
General）.

Kazunori KATAOKACOINS Research Leader/Director General,
Innovation Center of NanoMedicine,
Kawasaki Institute of Industrial Promotion
Professor, The University of Tokyo

The ideal is that our health ismaintained without us
knowing and cure illness
In COINS, using a technique called backcasting, we first
formed a concept upon picturing an ideal society and whatsteps are needed to get there, and what we should do andhow we can use the science and technology that we haveat hand.
We are adopting the concept of“In-Body Hospital”toimplement a‘smart life care society’and aim to develop
nanomachines（Figure 1）.
Currently, in order to cure diseases,‘people’such as
medical personnel, care workers, families who nurse,‘goods’such as medicines and medical equipment,‘places’such as hospital,‘money’to foster medical expenses
and medical personnel, and resources like waiting timeand‘time’until healing are becoming commonly used inlarge quantities. Detriments to society like retiring fromwork after becoming ill have also been occurring.
People go to hospital because they notice sickness. Our
health is also checked so we don’t become sick or we are
diagnosed and treated to heal our sickness so it is desirable that individuals consciously and actively participate in
medical treatment.
The COINS aim of a‘smart life care society’preferably
does not require these resources or individual awareness,that is to say, without knowing it, we are aiming for a soci2 | NanoSky VOL.02 DECEMBER 2016ety where health is cleverly maintained anytime, anywhere for everyone and where illness is cured. Ultimately,
the concept is that‘there is a hospital in the body of individuals and they cure themselves’=“In-Body Hospital”.
For example, this does not mean‘to not get cancer’but
rather a state where‘we are not afraid of getting cancer’.
People demand high quality medical care. This is only
natural as human beings. At the same time, costly drugs
put pressure on medical costs and society is becoming sensitive to the cost burden of treatment and the maintenanceof health.

Figure 1. Aiming to implement “In-Body Hospital”

In COINS we aim to achieve InBody Hospital where all medical
functions are integrated. Virus-sized
smart nanomachines autonomously
patrol the in-body microenvironmentand carry out treatment and diagnosis for 24 hours.

In the case of cars, for example, some of the technology
used for the development of the fastest cars, such as Formula 1® or some sports cars, is commonly incorporated
into popular cars while bearing the cost in mind.
The development of the latest preventive and therapeutic methods are also a huge cost in medical care and it isnatural for this to become significant, so it is also important to make it more acceptable by cost reduction and industrialization. It is necessary to reconcile these 2 conflicting directions. I would like to support this with technology
and concepts which have been researched and developed
in COINS.

Development of nanomachines toreliably reach affected areas anddemonstrate the function
The COINS concept of“In-Body Hospital”cannot be
achieved overnight. To this end, COINS initially targeted
diseases which have become major social and economic
problems and is dealing with 6 themes.
Of these, themes 1-5 aim to develop‘nanomachines’tosolve the problems. When looking at from the perspectiveof engineering, these nanomachines deliver, sensing, processing and operate these functions.
The reason for the 2016 Nobel Prize in Chemistry wasfor‘fundamental research to imitate the mechanical mechanisms of molecules’. Research and development of molecular machines capable of repeating the same operation by
application of physical/chemical stimuli such as light or achange in pH to a small molecule has been evaluated globally.
Immunity in the body is a similar molecular machine,each molecular machine works together creating a won-

derful system which can be used repeatedly.
Even the nanomachines we have developed are aggregates of the same molecules, they are intended for delivery, detection, diagnosis and treatment and may be referred to as more advanced molecular machines. Theseadvanced molecular machines become a resource for“InBody Hospital”. In the same way, a home-delivered pizza
not only brings the pizza but also changes the toppings according to customer's requirements and cleans the plate（remembering the customer's preferences and always providing the same service）.
Among the 6 themes, theme 1 affects about half the Japanese population, and for cancer, which is the cause of 1 in
2 deaths, accumulated research until now has aimed tocreate nanomachines that go beyond the anticancer
drug-encapsulating polymeric micelles which are in clinical
trials.
Anticancer agents have the characteristic that the effective dose range and the dose range in which side effects
appear are narrow so, by using nanomachines and being
certain to deliver an appropriate amount to the affected
part, the effect can be increased and the side effects reduced. We already know that delivery can be achieved tosome extent so we are now conducting research to further
improve the delivery accuracy and encapsulate anothertherapeutics such as nucleic acids.
To create a highly versatile treatment system which canbe used by anyone, anywhere, anytime, we believe theneed for nanomachines to deliver medicines, which matchthe individual cancer patient to the affected area is increasing more than ever. If nanomachine technology advances, there is the possibility that drugs which have notbeen used thus far because of side effects will be used andnot just for cancer. Initially delivering medicines thendemonstrating function. We would like to approach step bystep to‘implementing a smart life care society’.

Figure 2. COINS Vision and Mission

NanoSky VOL.02 DECEMBER 2016|3

Talking about
Theme 1To Design the Next
Anticancer Drug-Encapsulating
Polymeric Micelle
The mission of COINS theme 1 is to evolve anticancer drug-encapsulating polymeric micelles which are
1deliverythe basis of the concept of In-Body Hospital and to create the next generation of DDS＊（drugsystems）. The theme 1 leader, Associate Professor Kanjiro Miyata of the Department of Materials
Engineering at The University of Tokyo and the Center for Disease Biology and Integrative Medicine,
Graduate School of Medicine, The University of Tokyo, Tetsuya Hamaguchi, Medical Director of the
Department of Gastroenterology in the National Cancer Center Central Hospital who is involved in theclinical development of anticancer drug-encapsulating polymeric micelles in Japan and Kenichiro Naito,
Director of Research Division in NanoCarrier Co., Ltd. talked about the current research and future
progress.

Tetsuya HAMAGUCHI

Kanjiro MIYATA

Kenichiro NAITO

Medical Director,
Department of Gastroenterology,
National Cancer Center Central Hospital

Associate Professor,
Department of Materials Engineering
Graduate School of Engineering,
The University of Tokyo

Director of Research Division,
Head of Discovery Research,
NanoCarrier Co., Ltd.

A resident in the National Cancer ResearchCenter Department of Internal Medicine andstudied under Dr. Yasuhiro Matsumura of the
Exploratory Oncology Research & Clinical Trial
Center at the National Cancer Research Center
East Hospital. Involved in clinical studies ofanticancer drug-encapsulating polymeric micelles.
Also involved in the management of the multiinstitution, collaborative clinical studies group in
the colon cancer group executive office of theJapan Clinical Oncology Group and has also
assisted research representatives/the research
executive oﬃce in several phase III studies.

Gained PhD (engineering) under the guidanceof Professor Kazunori Kataoka in 2006 in the
Department of Materials Engineering, Graduate
School of Engineering, The University of Tokyo.
S u b s e q u e ntly b e c a m e a P roje ct A s sis t a nt
Professor in the Department of Bioengineering,
Graduate School of Engineering, in 2009 moved
to the Center for Disease Biology and Integrative
Medicine as an Assistant Professor and in 2013
promoted to Associate Professor. Transferred to
the Department of Materials Engineering, Graduate
School of Engineering in 2016 and presided over
the research laboratory. The main research topic
is the development of nucleic acid-encapsulating
nanomachines based on polymeric materials .

Research Division Manager in the Research
Division of Nanocarrier Co., Ltd., and responsible
for the investigation laboratory and nonclinicalevaluations (for about 3 years). In previous job (ina major Japanese pharmaceutical company), led
the overall research strategy planning after involvedin cancer drug research and strategy planning.
Currently devoting efforts to transitioning to theearly clinical stage of antibody-bound polymeric
micelle No. 1 which will be the next-generation
technology and advancing application of thesame technology to intractable cancer jointlywith Matsumura s group in the National Cancer
Research Center and iCONM. Also supporting theearly approval of drugs during clinical trials from thenonclinical standpoint.

4 | NanoSky VOL.02 DECEMBER 2016

Increased accumulation of
drug at a cancer site using
anticancer drug-encapsulating
polymeric micelles bound toanti-TF antibody■ Please introduce your current work.
Miyata: In theme 1, I am creating nanomachines whichtarget cancer. When I was in the Kataoka Laboratory,
the development of polymeric micelles encapsulating
anticancer drugs（Figure 1）had been advanced considerably. So, Iʼve taken on researching new polymeric micelles which contain nucleic acid drugs.
Hamaguchi: Iʼm a medical oncologist in the Department
of Gastrointestinal Medicine at the National Cancer
Center Central Hospital. I met Dr. Yasuhiro Matsumura（Exploratory Oncology Research & Clinical Trial Center in the National Cancer Research Center）when I
became a hospital resident in 1997 and from the outset
I was involved in clinical studies of doxorubicin（Adriamycin）-encapsulating polymeric micelles until 2002. I
also took my pre-clinical studies with Dr. Matsumura.
Subsequently, as a clinician I specialised mainly in the
drug treatment of colon cancer and I also conduct clinical studies.
Naito: I was engaged in anticancer drug research in a
big Japanese pharmaceutical company for more than
30 years, for about the past two and a half years Iʼve
been in charge of the research of the ﬁrst and the next
generation of anticancer drug-encapsulating polymeric
micelles and subsequently polymeric micelles in NanoCarrier Co., Ltd.
Figure 1.
A Polymeric Micelle Encapsulating an Anticancer Agentpolymeric micelle. ʻWhat is not workingʼ with the current polymeric micelles, as well as anticancer agentsand molecular target drugs, is likely to be the key tocreating new nanomachines. For example, we are considering targeting brain tumors and pancreas tumors
which are hard to reach by anticancer agents.
Naito: Depending on the most diﬃcult part, to create a
new nanomachine, on Prof. Miyata, NanoCarrier is focusing on the clinical development of the ﬁrst generation nanomedicine and the nanomedicine attached toan anti-tissue factor antibody（anti-TF antibody）*2 which
acts as a sensor for cancer tissue as the second generation. Iʼd like to get this targeted polymeric micelle intoa clinical trial next year or the year after.
In actual fact, slightly changing the chemical structure and administration method increases the efficacy andmay decrease side ef fects .
When aiming at technicallydiﬃcult things, I think using adrug well-known its effects
and mechanism is a short cut
to make a good nanomedicine.
Miyata: Mass production is difficult when academia creates
fancy materials from a narrow
vision as they may well be materials which cannot be put
into practical use. We will
steadily continue our research
to avoid this.

It is also possible to encapsulate
existing anticancer drugs intopolymeric micelles■ What kind of effect can be expected from a
combination of an anticancer drug-encapsulating
polymeric micelle and an anti-TF antibody?

■ What about the position of theme 1 in this COI
program?
Miyata: The goal is to create newer and better nanomachines than the ﬁrst-generation of polymeric micelleformulations which are already in clinical trials. “InBody Hospital” cannot be achieved by even slightly
changing the encapsulated drugs or modifying the

Naito: Accumulation of first-generation polymeric micelle formulations in cancer tissue is higher than for
the anticancer agent encapsulated in micelle itself due
to the EPR eﬀect（Figure 2）. However, micelles attached
to anti-TF antibodies more easily accumulate in cancer
because of the action of the antibody. Therefore, combining these two（micelle and antibody）will further increase the rate of accumulation in cancers.
Miyata: Anti-TF antibodies can recognize not only thecancer cell surface but also the cancer-related stromal tissues. For that reason, they can target a wide scope ofcancers which do not express speciﬁc markers on theirsurface. This ﬁts the concept of “In-Body Hospital” whichtargets a variety of speciﬁc tissues.
Naito: The number of anticancer drug molecules at-

NanoSky VOL.02 DECEMBER 2016

|5

TALK
tached to one antibody is usually limited to 3 or 4,
when an anti-cancer agent is directly bound to an antibody but the amount of drug which can be carried by
one antibody will be 100 times that or more when micelle technology is applied. This expands the choice ofdrug, its action and its dose.
Hamaguchi: Unlike animal experiments, when drugs
are actually used clinically the individual diﬀerences incancer cells are marked even in the same cancer andthe same person depending on the disease condition. If
you can make new drug candidates that are highly effective and gather safely, we will evaluate ﬁnely how to
use clinically. Iʼm looking forward to it.
Although the number of drugs for colorectal cancer,
which I specialize in, has increased and standard treatment changed around 3 years ago, there havenʼt been
so many new drugs since then. A breakthrough is also
necessary in the treatment of stomach cancer. Scirrhous gastric cancer, which advances rather rapidly

and has a poor prognosis, metastasizes to the peritoneum and is prone to ﬁbrosis, thereby showing the characteristic that drugs can barely reach it, similar to pancreatic cancer. Thus, if pancreatic cancer can betreated with drug-encapsulating polymeric micelles,
then I expect that they can also be used for scirrhous
gastric cancer.
Naito: As a venture company and in terms of development cost and time, Iʼd like narrow down cancer targets in consultation with Dr. Hamaguchi and other clinicians and manufacturers of diagnostic agents.

Hamaguchi: Immune
checkpoint inhibitors
were initially approved
for melanomas then forlung cancers considering the characteristics
of such cancer and thismeans using them whileca ref ully monitor ing
their mechanism suchas pharmacokinetics incancers for which there
are no treatments.

■ It is considered that anticancer agents which
could not be used until now because of strong side
effects can now be used by encapsulation inpolymeric micelles.
Hamaguchi: Although individualized treatment using
biomarkers to predict the therapeutic eﬀects and side
effects of drugs is now progressing, there are many
cancers which cannot be classiﬁed and, in this instance,
they are treated using evidence-based anticancer
agents as in the past. The therapeutic eﬀects and side
eﬀects may change depending on the length of the administration period even with for the same anticancer
agent but the side eﬀects can be lessened by encapsulation in a polymeric micelle and drugs which could not
be used can now be. For example, neurological impairment occurs with platinum formulations in about 6
months due to their accumulation. Because polymeric
micelle formulations markedly accumulate in cancer
tissue there is the chance that they wonʼt accumulate
in the nerves.
Miyata: Resistant cancers may not be cured even if apolymeric micelle which contains an existing anticancer
drug can reach it. In this case, new drug candidates
which are expected to have a synergistic eﬀect when in
combination are encapsulated in polymeric micelles and itis thought that it is better to accumulate 2 diﬀerent drugs
in the cancer in the same proﬁle（see p. 8）. In this way,
existing cancer agents may also show eﬀectiveness.

Figure 2. EPR Eﬀect（Enhanced Permeability and Retention Eﬀect）

Angiogenesis and the permeability of the blood vessel wall
are aggravated in cancer tissuecompared to normal tissue andit is known that macromolecular
substances readily accumulate
because the lymphatic system
which discharges these macromolecules has yet to develop.

6 | NanoSky VOL.02 DECEMBER 2016

Laboratory, which is doing joint research with NanoCarrier, is also carrying out animal experiments here.
We are using our lab as a forum for discussion andconducting research together here.

■ iCONM is seen as becoming a third place
and a co-working space . Finally, please tell us
about your future ambitions.

It is important for engineeringresearchers to share
information and cooperate withclinicians and companies
Miyata: Theme 1, in particular, is strongly connected tosociety and we can recognize the current problems
when talking and cooperating with clinicians and companies. It is important for researchers in the ﬁeld of engineering to understand, share and think together
about the dose and administration period. There is adeluge of articles at our research site stating that ʻifnanoparticles are made with a diameter of around 100 nm
then they will all accumulate in the cancerʼ. However,cancer tissue is, in fact, diverse so the size eﬀect willvary greatly depending on the type, site and stage.
Therefore I think research into the tissue permeabilityof nanomachines will become valuable in the future（see p.10）. It may only be about size but size is really
important in the development of nanomachines. We areaware of designs which do not end up as research in
published articles. Based on the objective of “In-Body
Hospital”, we would like to promote research from both
perspectives of forecasting while backcasting which advances one step at a time based on our technology. If it
is evidenced that the amount of drug which accumulates speciﬁcally in the target disease site is increasedby using targeting ligands, such as anti-TF antibodies,then I think it will also pay oﬀ in research into a breakthrough in blood-brain barrier work in theme 2 as well
as for theme 1.

■ What s your impression of coming to the iCONM?
Miyata: When I come here, I talk with people working
on other research themes and I am able to talk to specialists in various ﬁelds as well. Thereʼs equipment here
not found in university laboratories. The hurdle whenstarting joint research is low so Iʼd like to get started
soon because new ideas for collaborative research are
now emerging.
Hamaguchi: Today was my ﬁrst visit. I could get an
idea of the initial stages of drug R&D.
Naito: NanoCarrier has our lab here. Dr. MatsumuraʼsMiyata: In the nanomachines enveloping nucleic aciddrugs currently being developed, the size is controlled
to 1-2 nm and we are checking that that size is maintained in vivo . I would like to carry out a detailed investigation of how those nanomachines enter cancer
tissue and cancer cells and clarify what kind of parameters are necessary and what kind of technology isnecessary to strike at intractable cancer.
Hamaguchi: Iʼd like to keep drawing out the goodqualities of drugs and assist in the spread of new drugs
around the world while being involved from the earlystage of drug development. We are more than happy
for a drug to be eﬀective, to have few side eﬀects andfor treatment to be maintained.
Naito: As a bridge between
the nanomedicines which aredeveloped by Prof. Miyata andthe clinicians like Dr. Hamaguchi, NanoCarrier would like tomodify the nanomachine to getgood results in clinical and tosupport clinical development if
required, and also would liketo improve the nanomedicine
by considering the requestfrom clinicians.
Miyata: A strength of this project is that you can cooperateright from the start through tothe end.

■ Many cancer patients are waiting for highly
effective drugs with few side effects. I expect R&D
to progress further.
（ Interviewer： science writer Ayumi KOJIMA ）Terminology＊1 DDS
Abbreviation for Drug Delivery System. A general term for technology aimed
at increasing the therapeutic eﬀect of physiologically active substances,such as genes and drugs like anticancer agents and contrast agents, and at
reducing side eﬀects by allowing them to act at the required site and at therequired dose when necessary .
＊2 Anti-tissue factor antibody
Tissue factor（TF）is an exogenous blood coagulation initiation factor, which
is often expressed in cancer cells and in the blood vessels in cancer tissue.
TF is expressed in many cancers, such as pancreatic cancer and brain
cancer, and the higher the expression of TF the higher the malignancy
and poorer the prognosis. Therefore, it is expected that the development ofanti-TF antibodies and DDS-targeting TF will lead to eﬀective treatment of
intractable cancers.

NanoSky VOL.02 DECEMBER 2016|7

Reserch
Highlights

1

Theme 1

Success in Developing a Nanomachine
Targeting Cancer Stem Cells＊1～ conﬁrming success of a model of exposure to asbestos＊2
leading to malignant mesothelioma ～Standard treatment for malignant mesothelioma caused by exposure to asbestos has yet to be establishedand the development of new cancer drugs is awaited. We have succeeded in developing nanomachines which
selectively accumulate in malignant pleural mesothelioma tissue and release drug into cancer cells to treat
them. Based on this result, I expect that we can contribute to the establishment of an eﬀective treatment forrefractory cancers like mesothelioma in the future.

Hiroaki KINOH
Deputy Head/Principal Research Scientist,
Kataoka/Kinoh Laboratory,
Innovation Center of NanoMedicine,
Kawasaki Institute of Industrial Promotion

Horacio CABRAL
Associate Professor, Department of Bioengineering,
Graduate School of Engineering,
The University of Tokyo

It is known that conventional cancer treatments likeanti-cancer drugs. This novel polymeric micelle was in-chemotherapy and radiotherapy are not successful in

travenously administered to a malignant pleural meso-

treating malignant mesothelioma and it is thought thatthelioma mouse model ＊5 and the survival rate wasmany cancer stem cells are present. Therefore, theinvestigated to conﬁrm the therapeutic eﬀect of stauros-development of therapeutics for cancer stem cells inporine/epirubicin-encapsulating polymeric micelles onmalignant mesothelioma is being carried out vigorously

malignant mesothelioma. As a result, all animals in the

all over the world at the moment.

untreated group died after 1 month and all animals in

By confirmation using aldehyde dehydrogenase

the epirubicin group died after 2 months. Death of 70 %（ALDH）, which is known as a cancer stem cell marker,

or more animals was conﬁrmed in about 3 months in the

we have found that there are many cancer stem cells in

epirubicin-encapsulating polymeric micelle treatment

malignant mesothelioma. Subsequently, as a result of angroup, while survival of all mice was conﬁrmed even af-

investigation into substances which are eﬀective against

ter 3 months in the staurosporine/epirubicin-encapsu-

cancer stems cells using this activity as an indicator, it

lating polymeric micelle treatment group（Figure 2）.

has been found that the cancer stem cell killing eﬀect ofMoreover, recurrence of cancer was not seen in half or＊3

staurosporine is very high.

more of individuals even 9 months after discontinuation

Staurosporine, however, is barely soluble in water andof administration.

that it is deactivated in blood. When trying to encapsu-

These results suggest that a formulated nanoma-late staurosporine in a polymeric micelle to overcome

chine containing a combination of existing anticancer

this problem, it was found that it can be eﬃciently en-

drug and staurosporine is suitable in the eﬀective treat-＊4veloped in epirubicin-encapsulating polymeric micelles

ment of cancer tissues in which many cancer stem cells

which our research group have already made. Theseare present. In fact, it has been conﬁrmed that stauros-

staurosporine/epirubicin-encapsulating polymeric mi-porine/epirubicin-encapsulating polymeric micelles show

celles respond to the low pH environment in and aroundmarked eﬃcacy against other cancers（such as lung can-cancer cells and the release of staurosporine was cor-cer, stomach cancer and breast cancer）.

related with the release of epirubicin（Figure 1）.

We would like to contribute to the establishment of

We have further conﬁrmed in cell experiments thatan eﬀective treatment for highly malignant cancer giv-

these polymeric micelles are also effective against

ing rise to recurrence and metastasis by expansion ofcancer-stem cells, which are resistant to treatment withthese results in the future.

8 | NanoSky VOL.02 DECEMBER 2016

Figure 1. Development of Novel Nanomachines

Epirubicin is chemically bound to a block co-polymer.
Staurosporine is, however, encapsulated in polymeric micelles
without chemical bonding by a mutual interaction with
epirubicin. In the mechanism of drug release within cells by
pH-responsive polymeric micelles, it is known that (1) micelles
enter cells via vesicles made of collapsed membrane known

as endosomes, (2) chemical bonds dissociate due to a pH
decrease within endosomes, and (3) drug is released frommicelles, and the novel polymeric micelle in this study canrelease epirubicin and staurosporine within cells by the samemechanism.

Figure 2. Eﬀects of Novel Nanomachines against a Mouse Model of Malignant Pleural Mesotheliomaa. Treatment group not shown in the ﬁgure will be supplemented. The survival
rate in the treatment group administeredwith a combination of EPI and STS atabout 2 months was 0% and in the treatment group administered a combinationof EPI/m and STS the survival rate fell
to below 30% after 3 months, which was
similar to the EPI/m treatment group.
b. Blue-red line is the tumour detection
site. The presence of a tumour was conﬁrmed in almost all mice except those in
the STS/EPI/m treatment group.

Terminology＊1 Cancer Stem Cell
It has recently been thought that cancer tissue is not a population of single cells
but many cancers grow from a few cancer stem cells . Cancer stem cells are
known to be resistant to conventional cancer treatments like anticancer agents andradiotherapy. Therefore, tissues containing many cancer stem cells are thought to behighly malignant cancers which are liable to cause recurrence and metastasis.

＊4 Epirubicin-encapsulating Polymeric Micelle
Epirubicin is a kind of anticancer agent and exhibits an antitumour effect bybinding to DNA in cancer cells and inhibiting gene synthesis. Epirubicin micelles
refer to polymeric micelles in which epirubicin is encapsulated by numerous block
copolymers (see Figure 1). This micelle is currently in a phase I study and ismoving towards practical application.

＊2 Malignant Mesothelioma
A disease in which malignant (cancer) cells are formed in the membrane covering
the inner thoracic cavity or peritoneal cavity. It is a highly malignant cancer andmost suﬀerers die within 1 year of contracting it. A major cause is aspiration ofasbestos and the greater the exposure to asbestos and the longer the period,
the greater the risk of onset. Malignant pleural mesothelioma refers to malignant
mesothelioma which develops in the membrane (pleura) which covers the insideof the lungs and thorax.

＊5 Mouse Model of Malignant Pleural Mesothelioma
Mice inoculated into the thoracic cavity with malignant mesothelioma cells andwhich artiﬁcially suﬀer from malignant pleural mesothelioma.

＊3 Staurosporine
It is known that Dr. Satoshi Omura (Nobel Prize in Physiology or Medicine in2015) discovered an antibiotic which strongly induces apoptosis (cell death). It
has potent side eﬀects as it also aﬀects normal cells so has not been put into
actual use in cancer treatment but it can be considered to be a potent anticancer
agent if it can be delivered to cancer cells only.

References
H. Kinoh, Y. Miura, T. Chida, X. Liu, K. Mizuno, S. Fukushima, Y. Morodomi, N.
Nishiyama, H. Cabral, K. Kataoka, Nanomedicines eradicating cancer stem-like cells
in vivo by pH-triggered intracellular cooperative action of loaded drugs. ACS Nano
10 (6) 5643-5655 (2016)

NanoSky VOL.02 DECEMBER 2016|9

Reserch
Highlights

2

Theme 1

Discovery of a New Tumor Blood Vessel
Permeation Pathway to Increase
the Eﬃcacy of DDS in Cancer!
We have discovered an extremely dynamic phenomenon in which spatiotemporally irregular collapse occurs in
the tumor blood vessels and eruption of polymeric micelles into extravascular cancer tissue.
If we can elucidate the mechanism of phenomena and make use of it, it is expected to lead to the developmentof a new drug delivery method especially one for intractable cancer [1].

Yu MATSUMOTO
Assistant Professor, Department of Otolaryngology,
Auditory and speech surgery
The University of Tokyo Hospital

Tumor blood vessels are known to be fragile andmeric micelles which have high retention in blood, wehighly permeable. A general concept about the EPR eﬀect

realized the acquisition of spatiotemporal information of[2]

in the pastso far （see p. 6, Figure 2）is that there are intracellular spaces and highly permeable pores referred as

the distribution pattern of DDS in the tumor.
The results of image analysis and computer simula-fenestrations in the tumor blood vessel and it is said thattion following administration of 2 types of polymeric mi-

macromolecular substances gradually leak out of bloodcelle with diﬀerent diameters showed that the incidence

vessels via these. Many DDS preparations（see p. 7）of eruption correlates with the distance between thedemonstrate antitumor effects using this EPR effect.

blood vessel and the tumor, the speed of eruption uses

However, the fact is that DDS preparations cannot achieve

the pressure diﬀerence inside and outside the tumor as

the ideal therapeutic eﬀect against intractable cancers

a driving force and that diﬀusion after eruption is con-such as pancreatic cancer and scirrhous gastric cancer.

trolled by interstitial density.

One reason is thick interstitial formation which isThis study newly advocates ʻeruptionʼ from ʻdynamic

characteristic of intractable cancer. It is understood thatventsʼ which open and close for a short time rather that

DDS with a large particle diameter cannot penetrateʻstatic poresʼ（Figure 2）. If we can elucidate the mechanism

the interstitium so they remain around the blood vessel.

of eruption and induce or suppress it in future research,

Kataokaʼs research team has shown that the intersti-

it may become possible for the DDS preparation to eﬃ-[3]tium can be penetrated by reducing the particle size .
In this study, we observed the distribution of polymeric micelles within the tumor in detail over the longterm and at short imaging intervals. As a result, wehave discovered an extremely dynamic phenomenon inwhich spatiotemporally irregular collapse occurs in thetumor blood vessels and eruption of polymeric micelles
into extravascular cancer tissue.（Figure 1）.
Although eruption is a phenomenon which is converged within approximately 60 minutes and was once
was impossible to capture with the histological methodwith conventional ﬁxed thinning, due to our recent efforts, by mouse anaesthesia management and imaging
technology have improve [4] and by development of poly-

10 | NanoSky VOL.02 DECEMBER 2016

ciently reach cancer tissue. It is expected that this willlead to new treatment methods for intractable cancer.
References[1] Matsumoto, Y., Nichols, J. W., Toh, K., Nomoto, T., Cabral, H., Miura, Y.,
Christie, R. J., Yamada, N., Ogura, T., Kano, M. R., Matsumura, Y., Nishiyama, N.,
Yamasoba, T., Bae, Y. H., Kataoka, K., Vascular bursts enhance permeabilityof tumour blood vessels and improve nanoparticle delivery, Nat Nanotechnol,
2016, 11, 6, 533-538[2] Matsumura, Y., Maeda, H., A new concept for macromolecular therapeutics
in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins
and the antitumor agent smancs, Cancer Res., 1986, 46, 12 Pt 1, 6387-6392[3] Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M.,
Terada, Y., Kano, M. R., Miyazono, K., Uesaka, M., Nishiyama, N., Kataoka, K.,
Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours
depends on size, Nat Nanotechnol, 2011, 6, 12, 815-823[4] Matsumoto, Y., Nomoto, T., Cabral, H., Matsumoto, Y., Watanabe, S.,
Christie, R. J., Miyata, K., Oba, M., Ogura, T., Yamasaki, Y., Nishiyama,N., Yamasoba, T., Kataoka, K., Direct and instantaneous observation of
intravenously injected substances using intravital confocal micro-videography,
Biomed Opt Express, 2010, 1, 4, 1209-1216

Figure 1. Exploring the cases of eruptionseruption state

Polymeric micelles show good retention in the blood,
therefore tumor blood vessels can be identified byfluorescent labelling. Polymeric micelles erupt rapidly
from part of the tumor blood vessel in a pancreaticcancer model（0 min）and immediately spread to thesurrounding tissues. Eruption is over in 30-60 minutes

and polymeric micelles leaving the blood vessel
continue to diﬀ use. Major eruption（0 min, red frame）
near the center of the angle of view, and small eruption（110 min, green frame）at another area somewhat to
the right.

Figure 2. Images of ʻStatic Poresʼ and ʻDynamic Ventsʼ

NanoSky VOL.02 DECEMBER 2016

| 11

Listen to

COINS'
MemberYuki MOCHIDA
In order to find a drug which completely
cures all kinds of cancers, I am designing
nanomachines for dlug delivery and evaluating
their function and eﬀectiveness.

I and grew up in Tottori, a garden city.

was born in Osaka, a city of merchants,

An ideal city for me is a convenient placewith access to the main stations in Tokyo
while being side by side with vibrant shopping streets and abundant nature. Searchingfor such an ideal city has become my holiday hobby over the past few years and I am
going to various areas in Tokyo and enjoying
exploring the city. When you actually visit thecity and sense its atmosphere, you can understand the real quality and personality of acity which you cannot do from informationfrom the internet. In particular, my instinctive
impression of a city often captures its essence and this is what I value most. As intu-

Sabina QUADER

Senior Reseach Scientist, Kataoka/Kinoh Laboratory,
Innovation Center of NanoMedicine,
Kawasaki Institute of Industrial Promotion

Increasing insight, pursuing an ideal
ition is usually based on past comprehensive
experience and knowledge, if there is no experience and knowledge in the first place
then it s no different from a wild guess. In order to increase the accuracy of intuition andfor it to be a really useful reference, we needto acquire experience and knowledge on aregular basis. Even in my research on cancer-targeted nanomachines, I occasionallycome up with new designs of nanomachines
which I intuitively feel are successful throughtrial and error. To prevent such ideas fromsinking into obscurity, of course, I hope to increase the accuracy of insight by step bystep accumulation of knowledge and experience and contribute to the achievement of aam from Bangladesh. I was born andcity of Bangladesh. After ﬁnishing my MSc
degree in Chemistry, I started working as alecturer at Chittagong University of Engineering and Technology. After two years ofteaching, I accepted a PhD scholarship offerfrom Griffith University, Brisbane, Australia
and subsequently completed my PhD there.
I came to Japan in 2010 with a JSPS postdoctoral research fellowship and joined
Professor Kazunori Kataoka s laboratory（kklab）at the Material Engineering Department of Tokyo University. In 2015 I became
the Senior Research Scientist in Kataoka/
Kinoh laboratory at the Innovation Center of

12 | NanoSky VOL.02 DECEMBER 2016

smart life care society by creating high-performance nanomachines which form thecore of next-generation medical care.
Incidentally, as a result of a fervent pursuitof my ideal city in Tokyo, I started living in
Kawasaki city in Kanagawa prefecture.

Members in Kataoka/Kinoh lab from around the world
together.

Senior Research Scientist, Kataoka/Kinoh Laboratory,
Innovation Center of NanoMedicine,
Kawasaki Institute of Industrial Promotion“Humanity” always leads
my scientif ic enquiries
I raised in Chittagong, the largest port

What w

NanoMedicine（iCONM）. I am conducting
research with a focus on developing nanomedicines for diagnosis and treatment of
intractable cancers. I feel privileged to beable to get involved in research activities
under the direct guidance of Professor
Kataoka, a world-leader in the ﬁeld of drugdelivery system.
I live in Japan with my husband who is awriter, researcher and filmmaker and my
9-year-old daughter. Unfortunately my Japanese skill is poor but my daughter who is
ﬂuent in Bengali, English and Japanese often helps as an interpreter. During our 6
years stay in Japan, we always sense a
feeling of security and sincerity. Japanese

I am developing novel nanotherapeutic drugs
eﬀective in many types of cancer. My current
research is particularly targeting brain tumours
and metastatic breast cancers which are hard
to reach tumours.

people are honest, warm and reserved;
overall Japan is a wonderful country. In Japan cutting-edge technology and tradition
exist side by side. This particular amalgamation of the modern with the traditionalfascinates me in every moment of my Japanese experience.

Together with my adorable daughter who
is brimming with curiosity.

e treasure
Masaru UENO

Chief Researcher,
4th Research and Development Team (liquid biopsy)
JSR Life Sciences Corp

Considering our own health will
spread new interests
U at COINS, I am trying to create a bignder the concept of In-Body Hospital

dream of prolonging a person s healthy life
span. There are many things to learn from thatbig dream although putting it into practice isstill ahead of us.
I recently watched the MBL news of Ichiro s
3000 hits and realised that a great record canbe created by maintaining a high level ofhealth over a long period. My feeling thatmaintaining a high level of health over a long
period is important has also become stronger
for my work in research and development.
With the practical use of In-Body Hospital
proposed by COINS which is currently being
developed in mind, I thought about what I can

do now to maintain health over a long period. I
ﬁnally then found simple answers and hit on
exercise and supplements and started toplay tennis, and, while trying to improve physical ﬁtness, I checked every day so see if theeffect of supplements had kicked in.
By exercising, my daytime mood was refreshed but at night I felt very tired so now I ve
begun to look for something else when I m
tired. It seems that it is a fascinating ﬁeld andit appears that the feeling of tiredness is probably due to stimulation of the brain by reactive
oxygen. For removal of active oxygen from thebrain, carnosine, which is dipeptide of β-alanine bound to histidine, can be purchased. I mvery interested in simple peptides which do

Tsukasa CHIDA
We aim to achieve innovative cancer treatment
and are carrying out research onto drugreleasing nanomachines.

W family .

hat I cherish is the time spent with myDuring my work while coming and going
between Kowa s Fuji Research Institute（FujiCity, Shizuoka Prefecture）and the Innovation Center of NanoMedicine（Kawasaki City,
Kanagawa Prefecture）, time spent with mywife and my son, who will be 1 this year, is irreplaceable time which heals daily fatigue.
On holidays, especially, I am trying to show
various scenes to my son whose expressionof feelings has become enriched and I sometimes walk on the Tama River bank next tothe Innovation Center of NanoMedicine.
When I think about it, the Innovation Center of NanoMedicine, which is the research

Although a liquid biopsy is attracting attention,
we are developing research reagents which
can be used in other fields and are promoting
translational research for diagnostic agents.

not have a complicated structure like polyphenols but demonstrate this effect, and I spend
the evening reading related articles while having a drink. As this is done until night time, I
get tired（fatigued）and I give my family a cold
look... . In future, research on how to eliminate
fatigue for health using In-Body Hospital isnecessary.

Three cute kids eating American corn dogs.

Researcher, DDS Group,
DDS Research Department, Fuji Research Laboratory,
Pharmaceutical Division, Kowa Company Ltd.

The achievement of “In-Body Hospital”
along with my childʼs growthbase of this COINS project, will celebrate
one year since its establishment. I felt expectation and trepidation about the birth of myﬁrst son and it was such a great year that thedays when I was engaged in establishing acollaborative laboratory between COINS andour company seemed like only yesterday.
Among the cutting-edge research facilities,
what can be achieved as a business? Although I started from the point of preparing
the research environment for this, I am moving forwards little by little while being supported by the staff of iCONM and seniors in
the workplace. Like my eldest son who stillcannot walk yet, Kowa s challenge for the future is just beginning.

When I think carefully about the future of
my family in the vision of COINS 20 years on
and when I think that In-Body Hospital has
to be achieved around the time my childbecomes an adult,
as a researcher bybody tenses at thesame time as the
feeling of expectation for the future
grows.

Shizuoka landmark - with myson at Mt Fuji.

NanoSky VOL.02 DECEMBER 2016

| 13

ACTIVITY REPORT
6th General Meeting
The COINS 6th General Meeting was held in the main conference
room at the Kawasaki Life Science & Environment Research Centre（LiSE）on Friday, June 3rd 2016.
The meeting is held every six months with the involvement of all participating institutions.
Each theme leader and participating institutions announced their intentions in what is to be done in the 2nd phase towards the achievement of
In-Body Hospital （declaration of intent） based on the results of the initiatives in the 1st phase（FY 2013 to 2015）.
Kawasaki City has reported on initiatives to create sustainable innovation based on the results thus far and future plans and prospects and the
COINS Research Promotion Organisation and the Kawasaki Institute ofPoster Session

Industrial Promotion have reported on the maintenance of compliance.
In addition, we set up poster sessions for research results and a lively
exchange of information exchange took place with 29 presentations.
We entered the 2nd phase and held a very meaningful general meeting
to further strengthen the tie up between the participating institutions towards achieving In-Body Hospital .

Discussion

Goings on in the whole venue

Topics2015.10 〜 2016.6◦10.30.2015 【Award】The laboratory of Takanori Ichiki, AssociateProf. (COINS theme 4 leader), Department of Bioengineering,
Graduate School of Engineering, The University of Tokyo (Takanori
Akagi, Nami Hanamura, Takanori Ichiki) received The Institute ofElectrical Engineers of Japan’s E Department of General Studies
Best Presentation Award at The Institute of Electrical Engineersof Japan. Award title:‘1 Particle Profiling of an Extracellular
Endoplasmic Reticulum in a Micropathway’.
◦12.5.2015 【Report】The joint research group of Takanori Ichiki,
Associate Prof., Department of Bioengineering, Graduate Schoolof Engineering, The University of Tokyo (COINS theme 4 leader)
et al and Nikon KK have developed the world’s first flexible opticalsheet sensor which can measure cellular oxygen metabolism without
damaging cells.
◦1.1.2016 【Newspaper】COINS and its core base Innovation Center of NanoMedicine (iCONM) was introduced in the hospital
newspaper.

14 | NanoSky VOL.02 DECEMBER 2016

Social Event◦ 1.4.2016 【Report】Keiji Itaka, Project Associate Prof., Graduate
School of Medicine Center for Disease Biology and Integrative
Medicine (COINS theme 3 leader), The University of Tokyo et al
held a press conference on their published article (Messenger RNA
delivery of a cartilage-anabolic transcription factor as a diseasemodifying strategy for osteoarthritis treatment, Scientific Reports).
Successfully curbed the progress of osteoarthritis. News article:
Nihon Keizai Shimbun, Wall Street Journal Japanese Edition, Toyo
Keizai ONLINE◦ 1.6.2016 【Newspaper】‘Nanomachines’and iCONM introduced
to the Asahi Shimbun and Asahi Shimbun DIGITAL. Title‘Not an SF
medicine dream’◦ 1.14.2016 【Report】Prof. Kazunori Kataoka (COINS Research
Leader) of The University of Tokyo Graduate School of Engineering
appeared on Asahi TV series Shinichi Hatori Morning Show’s‘Original
General Research Corner: anticancer drug treatment to a new stage’and explained nanomachines.

Activity Report◦ 1.30.2016 【Report】An interview article with Kazunori Kataoka(COINS Research Leader) Prof., Graduate School of Engineering,
The University of Tokyo was published in the March 2016 Editionof‘Chichi’. Title:‘This century’s achievement was accomplished tenacity and originality in the research and development of new drug
‘nanomachines’which will change the future of humankind -’◦ 1.31.2016 【Report】Kazunori Kataoka, Prof., Graduate School ofEngineering, The University of Tokyo (COINS Research Leader) appeared on the TBS series‘Running Doctor! Health Diagnosis Changes the Inevitable’and reported on an‘extremely small capsule which
destroys only cancer cells’.
◦ 2.1.2016 【Report】An article on COINS published in the February
issue of the monthly magazine‘Information Management’from
the Japan Science and Technology Agency. Promotion by industry/
academia/government/medicine/finance collaboration was introduced
and an outline of COINS’s initiatives from the three viewpoints ofinfrastructure, investment, and human resource development which
are important in building an innovation eco-system was given.
◦ 2.4.2016 【Report】Kazunori Kataoka, Prof., Graduate School of Engineering, The University of Tokyo appeared on the Asahi TV series
Shinichi Hatori Morning Show’s‘Original General Research Corner:
select cancer cells to destroy, radiotherapy front line’and explained
nanomachines (continuation of introduction to nanomachines broadcast on 14th January, 2016).
◦ 2.4.2016 【Activity Report】iCONM and the California NanoSystems
Institute (CNSI) cooperated closely and entered into a Memorandumof Understanding (MOU) regarding academic exchange.
◦ 2.5.2016 【Newspaper】‘Nanomachines’and iCONM introduced.
2/4 (Thursday) Yomiuri Shimbun evening publication‘SF actuallyenters the body and heals disease’, 2/5 (Friday) Nihon Keizai
Shimbun morning edition Regional Economic Aspect Kanagawa,'Innovation Center of NanoMedicine, Kanagawa’s Engine, IndustryAcademia-Government Collaboration in Advanced Medical Care,
Nanotechniques to Treat Cancer’.
◦ 2.15.2016 【Press Conference】Yu Matsumoto, Assistant Prof.,
Department of Otolaryngology, Auditory and speech surgery, The
University of Tokyo Hospital (COINS participating researcher),
Tatsuya Yamasoba, Prof. and Kazunori Kataoka (COINS Research
Leader) Prof., Graduate School of Engineering/Graduate School of
Medicine, The University of Tokyo et al held a press conference on
their published research theme (Nature Nanotechnology ‘Vascular:bursts enhance permeability of tumour blood vessels and improves
nanoparticle delivery’). Discovered a New Tumour Blood Vessel
Permeation Pathway to Increase the Efficacy of DDS (drug target
treatment) in Cancer!
◦ 2.18.2016 【Report】The research of Takanori Ichiki, AssociateProf., Department of Bioengineering, Graduate School of Engineering, The University of Tokyo (COINS theme 4 leader) introduced in
Kawasaki City’s Kawasaki SkyFront i-Newsletter Vol. 6 (February
2016 Edition).
◦ 2.22.2016 【Activity Report】COINS 5th General Meeting held.
◦ 2.29 to 30.2016 【Activity Report】Participated in the COI 2021
Conference sponsored by the Ministry of Education, Culture, Sports,
Science and Technology and supported by the Japan Science andTechnology Agency.
◦ 3.17.2016 【Report】An article from COINS research leader Kazunori
Kataoka published in a corner of the JST‘Journal of IndustryAcademia-Government Collaboration’‘Researcher Relay Essay’in
January 2016.
◦ 3.17.2016 【Award】Prof. Nobuhiro Nishiyama (COINS subtheme
5 leader) of the Chemical Resources Laboratory, Tokyo Instituteof Technology awarded the 3rd Particle Design Award from The
New Pharmaceutical Technology and Engineering Foundation, joint
awardee Prof. Kazunori Kataoka (COINS Research Leader) of The
University of Tokyo Graduate School of Engineering. Award title‘Development of a polymer micelle-type drug delivery system fortargeted therapy of intractable cancer’.

◦ 3.18.2016 【Activity Report】Published a newsletter‘NanoSky Vol. 1’.
◦ 3.23.2016 【Newspaper】Project Associte Prof. Kenji Itaka,(COINS theme 3 leader) et al of the Center for Disease Biology andIntegrative Medicine, Graduate School of Medicine, The Universityof Tokyo published an article in the Nikkei Business Daily on thetreatment of developing chondrodysplasia.
◦ 4.1.2016 【Activity Report】Held COINS Seminar No. 14 in iCONM.
◦ 4.5.2016 【Activity Report】Held COINS Seminar No. 15 in iCONM.
◦ 4.14.2016 【Report】Prof. Yoshihiro Muragaki et al of the Instituteof Advanced Biomedical Engineering and Science in Tokyo Women’sMedical University, a COINS participating institution, developed
sonodynamic therapy and published an article in the Nikkei Biotech
Online about starting clinical research within a year.
◦ 4.18.2016 【Report】Kazunori Kataoka, Project Prof., Policy
Alternative Research Center, The University of Tokyo, COINS
Research Leader (iCONM Centre Director), Hiroaki Kinoh, principal
research scientist and Horacio Cabral, Associate Prof., Graduate
School of Bioengineering, The University of Tokyo (iCONM visiting
research fellow) held a joint press conference with the University ofTokyo, iCONM and COINS on‘Success in developing a nanotech
anticancer drug aimed at cancer stem cells’regarding a publishedarticle from principal research scientist Hiroaki Kinoh (Kataoka/
Kinoh Laboratory Deputy Laboratory Director, visiting research
fellow at the University of Tokyo) (Nanotechnology journal publishedby The American Chemical Society, ACS ) (Nano : Nanomedicines
eradicating cancer stem-like cells in vivo by pH-triggered intracellular
cooperative action of loaded drugs).
◦ 5.8.2016 【Report】COINS research leader Kazunori Kataoka (Director of the iCONM and Project Prof. of Policy Alternative ResearchCenter, The University of Tokyo) appeared in the Japanese documentary programme‘Future Eyes’.
◦ 5.12.2016 【Activity Report】Held COINS Seminar No. 16 in iCONM.
◦ 5.16.2016 【Report】The University of Tokyo, iCONM, The Tokyo
Institute of Technology, the National Institutes for Quantum andRadiological Science and Technology and COINS held a joint press
conference on the‘Successful development of a‘nanomachine
contrast agent’for detection of tumour malignancy’regarding
an article published by Kazunori Kataoka, Project Prof., Policy
Alternative Research Center, The University of Tokyo, Director
General (COINS Research Leader), and principal investigator Mi
Peng, Nobuhiro Nishiyama, Prof., Tokyo Institute of Technology
and Aoki Ichio. Team Leader, National Institutes for Quantum andRadiological Science and Technology (Nature Nanotechnology : A
pH-activatable nanoparticle with signal amplification capabilities for
non-invasive imaging of tumour malignancy).
◦ 5.16.2016 【Activity Report】The 16th Symposium of Gene andDelivery Study Group held at LiSE.
◦5.25.2016 【Activity Report】Held COINS Seminar No. 17 in iCONM.
◦ 6. 3. 2016 【Activity Report】COINS 6th General Meeting held.
◦ 6.13.2016 【Activity Report】Held COINS Seminar No. 18 in iCONM.
◦ 6.14.2016 【Report] COINS research leader Kazunori Kataoka(Director General of iCONM and Project Prof. of Policy Alternative
Research Center, The University of Tokyo) appeared in‘Medical
Frontiers’on NHK World.
◦ 6.22.2016 【Report】A related article in a joint press conference
held on May 16th was featured in MEDTEC Japan Online as a special
report.
◦ 6.22.2016 【Report】Article by Project Prof. Kazunori Kataoka,
Policy Alternative Research Center, The University of Tokyo (COINS
Research Leader and Director General of iCONM) published anarticle in the Kawasaki Institute of Industrial Promotion’s‘Industry
Information Kawasaki June 2016’(published 1st June).

NanoSky VOL.02 DECEMBER 2016| 15

Editor s Note
In this NanoSky Vol. 2, we are focusing on eﬀorts and results
to support the creation of nanomachines in COINS theme 1
signiﬁcantly inhibiting cancer recurrence and metastasis . We
intend to introduce initiatives in each theme from hereon.
At the beginning of this journal, research leader Kazunori
Kataoka talked about the COINS vision of a smart life caresociety , In-Body Hospital which achieves it, the relationshipbetween the accomplishment ofgoals and eﬀorts of the

In-Body Hospitaland thetheme . I hope the top message will

help everyone understand.
COINS theme 1 aims particularly at establishing groundbreaking cancer treatment by refining the DDS function ofpolymer micelles which are the foundation of In-Body Hospital ,we have expanded much of the knowledge gained in theprocess to other themes, and this also plays an important roleas the driving force to promote R&D towards In-Body Hospitalin COINS overall.
From the trialogue and research topic 1 in this journal, theadvance in nanomachine development to change cancer
treatment with one eye on In-Body Hospital and from research
topic 2, I hope you are aware of the motivation of researchers intaking advantage of the potential of polymer micelles to obtainnew ﬁndings.
The next listen to COINS' members is a completely new
project and I hope to overcome the misunderstanding (?) of the
global negative image such being hard or tough for cutting-edge
researchers like this and to have affinity with members of
COINS.
The next issue aims at publishing on the theme of a cancer
diagnosis system in theme 4 in March next year. Please lookforward to it.
Last but not least, I would like to take this opportunity tothank members of the Editorial Committee and everyone for
their willing cooperation with this magazine despite the tightschedule. Thank you.
Chief Editor : Takashi SUGIMOTO

2

Edited by NanoSky Editorial Board ( Takashi SUGIMOTO, Kanjiro
MIYATA, Masahiro YASUNAGA, Kensuke OSADA and Yuki MOCHIDA)
Writer: Ayumi KOJIMA
Photograph: Aki TANAKA
Design: Studio L Co., Ltd.
Copyright: KAWASAKI INSTITUTE OF INDUSTRY PROMOTION

Vol.

Published by KAWASAKI INSTITUTE OF INDUSTRY PROMOTION,
Center of Open Innovation Network for Smart Health (COINS)
Research and Promotion Institute3-25-14, Tonomachi, Kawasaki-ku, Kawasaki City, Kanagawa Pref. JAPANTEL: +81 44 589 5785 / FAX: +81 44 589 5789
http://coins.kawasaki-net.ne.jp/