Japanese Ventures & the Future of the Economy
Interview with Mitsuko Sugano, Senior Fellow, Corporate Research & Development Center,Toshiba Corporation

Toshiba Applying Nanotechnology
in Search of Medical Remedies
By Japan SPOTLIGHT
Toshiba Corporation has a technological edge not only in IT but also in nanotechnology, as its principalproducts, infrastructure services, are today increasingly dependent upon devices or materials on anatomic, molecular and super molecular scale. With this technology, Toshiba can expand its R&D efforts incontributing to other businesses or even public policy. Health care is one of those areas.
We interviewed Mitsuko Sugano, senior fellow of the Corporate Research and Development Center ofToshiba Corporation and a leading scientist in their entrepreneurial project to apply nanotechnology to
medical remedies.
(Interviewed on Aug. 7, 2020)

Self-Introduction
JS: First, could you please tell us

about your career and thebackground of your project?

“Tumor-Tropic Liposome”
JS: Could you explain thecharacteristics of your “Tumor-TropicLiposome” technology?

Sugano: I am a specialist in biology and have
Sugano: What is most important in thebeen working on a wide range of research
application of gene therapy for cancers is to findprojects for Toshiba involving the use ofa technology for selectively introducing
molecular biology. One example is research on
therapeutic genes into cancer cells and not into
technology to detect harmful materials in thenormal ones. Precise delivery of therapeuticenvironment.
genes to the targeted cells would lead to an
Our newly developed “Tumor-Tropiceffective remedy.
Mitsuko Sugano
Liposome” which we announced on May 29,
The core element of Toshiba’s biodegradable
2020 is a gene therapy technology delivering therapeutic genes
liposome is a nano-capsule mainly consisting of lipids, devised with
developed by Shinshu University and containing “biodegradable
our own unique technology. This is a capsule about 100 nanometers
liposomes” – nano-sized capsules developed by Toshiba – to cancer
in diameter made out of lipids and this uniform-sized capsule cancells precisely and efficiently.
contain genes. Liposome itself has already been used for many
The background to the development of this technology is thatyears. We showed that optimizing the composition of lipids
cancer has been the leading cause of death in Japan for many years
enhances the probability of introducing therapeutic genes into theand the number of patients and fatalities continues to increase. Acancer cells selectively. Our newly developed nano-capsule isvariety of remedies have been discovered and tried and the survival
completely a chemically synthesized product and as such it is a safer
rate of cancer patients is increasing. However, the existing remedies’
and more efficient gene delivery technology than any othereffects are limited and a new remedy is required for cancers difficulttechnology used via a virus for the transfer of therapeutic genes in
to cure by surgery or medicine. One candidate for such a remedy isgene therapy so far.
gene therapy.
Shinshu University and Toshiba started joint research on theGene therapy is a remedy that needs extremely fine tuning, as it
utilization of biodegradable liposomes for delivery of therapeuticworks on cancer cells by delivering genes to those cells with the aim
genes without using a virus. We achieved 33-fold delivered genesof restoring their functions and strengthening them.
and 425-fold gene expression in therapeutic gene delivery to T-celltumors (T-cell acute lymphocytic leukemia), one of the cancers, asgreat as in delivery to normal T-cells (Chart 1). In short, weconfirmed that our new technology would create a great difference
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Japan SPOTLIGHT • November / December 2020

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Japanese Ventures & the Future of the Economy

CHART 1

Newly developed “Tumor-Tropic Liposome”

Selective gene delivery to cancer cells by biodegradable
liposomes
Unique, nano-sized biodegradable
liposomes developed by Toshiba
Artificial products mainly consisting of lipids
designed by Toshiba (patent applied)

Control of the lipid composition
achieves tropism
Gene expression(RLU)

Liposomal uptake

30000

(MFI)
600

Including DNA
or RNA

25000

500

20000

400

TEM image15000

100 nm
100 nm425-fold

300

10000

200

5000

100

033-fold

0

Tumor

NormalTumor

NormalSource: 2020 Toshiba Corporation

within the targeted cells.
In Shinshu University they had an experiment by using mice withhuman T-cell tumors transplanted. In one group of mice, theyinjected biodegradable liposomes containing cancer cell-killing genes
throughout their bodies through veins. Photos of the heat maps anda graph showing the increase in cancer days after liposome infusion(Chart 2) show very little increase in cancer in the group withliposome infusion until 13 days afterwards, and also show tumor
progression significantly suppressed even 21 days afterwards,
compared with the control group. We presented this result at ameeting of The American Society of Gene and Cell Therapy 2020 on
May 13 in 2020.
In our joint research, we proved that elaborated control of lipid
composition enables selective gene delivery to cancer cells.
Encouraged by this success, we would like to continue our joint R&D
to promote further improvements in gene therapy.

medical application. We were lucky to be introduced by chance toProf. Yozo Nakazawa at Shinshu University, one of the mostdistinguished and well-known experts on gene therapy without using
a virus, and he became interested in our biodegradable liposome
technology. That’s how our collaborative research began.
JS: With this new technology, do you think cancer canbe overcome?

Sugano: Gene therapy is still in the development stage and needs tobe much improved from now on. But with further efforts to advanceour technology, we would like to help enhance the options for
remedies for patients, in particular those suffering from cancers
difficult to cure.

Home Appliances & Healthcare

JS: Could you tell us how this collaborative research

JS: Toshiba is generally well known as an

Sugano: Toshiba had been working on R&D for biodegradable
liposomes for several years and thinking about its application in
health care, but we feared that achieving medical remedies might beout of our reach and we hesitated to explore that possibility of itsSugano: Toshiba defined precision medicine as a promising growthbusiness towards 2023 in our “Toshiba Next Plan”, our mid-termwith Shinshu University started?

66 Japan SPOTLIGHT • November / December 2020

infrastructure service company. How do you relate
your biotechnology business to Toshiba’s mainbusiness?

Japanese Ventures & the Future of the Economy

CHART 2

Verification of effects of tumor-tropic liposomes on micebearing T-cell tumors
Experimental
group

1.4

Control
group

1.2

1.0

0.8

107

0.6

0.4

0.2

0.1

Radiance(p/sec/cm2/sr)

Tumor [p/2/cm2/sr]

Days after liposome infusion

Controlgroup

Liposomes
infusion

Liposomes
infusion

Tumor progression
suppressedExperimental group

Color scale
Min = 1.10e6
Max = 1.35e7

Days after liposome infusion
Experimental Group: Administer biodegradable liposomes that contain therapeutic genes.
Control Group: Administer biodegradable liposomes that do not contain therapeutic genes.
On days 17 and 21, tumors in the experimental group show a significant level of suppression compared to the control group (p-value < 0.01)

Presented at ASGCT 2020 (May 13, 2020)
Source: 2020 Toshiba Corporationbusiness strategy published in 2018. Toshiba was originallycompetitive in technologies like nanomaterials and AI and we havebeen actively working on R&D to apply them to the medical andhealthcare business. In the R&D of biodegradable liposomes, wehave tried a wide range of nanomaterials to create nano-capsules. In
this process, we have taken advantage of AI’s function of mechanicallearning. I believe that AI is now a powerful tool that can speed up
R&D, and also that collaboration between AI and medical technology
will lead to technological progress in the medical and healthcare
business.
JS: Can biodegradable liposomes be referred to as

one of the most advanced technologies in Japan?

Sugano: Yes. We are pursuing the most advanced technologicalresearch in the sense that selective gene delivery to cancer cells
could be achieved without using a virus.
JS: Do you have a plan for collaborative research or abusiness partnership with an overseas research
institute in this area?

Sugano: We do not have any particular plan yet. However, seeingthat there are more publicly authorized technologies for gene therapy
overseas than in Japan, we are thinking about pursuing thepossibility of joint research with an institute in another country.

JS: With the positive outcome of joint research withShinshu University, are you planning to promote its
practical application or production on a large scale?
What issues would you need to tackle in the future?

Sugano: The outcome of our current experiments has only shown
the result of gene delivery twice to cancer cells by biodegradable
liposomes. We need to investigate the dose and times of delivery. In
addition, since the new lipid used for this experiment is a chemicallysynthesized product which has not existed before, we need toconfirm its safety over the long term for clinical use and find out
what types of cancers it can be most effectively applied to.
JS: As the aging of society continues in Japan, I

believe the medical and healthcare business has
great potential to grow.

Sugano: Yes, I think that is true. We believe that technologicaldevelopment in the medical area will be crucial for resolving various
social issues. We are not a pharmaceutical company, but we would
like to make a good contribution to overcome a wide range of social
challenges, including aging, by providing precision medicine such as
biodegradable liposomes for a variety of goals.

Written with the cooperation of Naoko Sakai who is a freelance writer.

Japan SPOTLIGHT • November / December 202067