good afternoon
my name is Stathis and I’m a biomedical
engineer and an associate professor here
at Case Western Reserve University so
today I’m going to talk to you about my
labs work on cancer nanotechnology and
our quest for the ultimate tract
smuggler so before I begin I have to
make a confession before I became a
biomedical engineer I was actually
trained as a chemical engineer in my
undergraduate schooling so when I look
at all of you I cannot help myself but
see a collection of pipes your blood
vessels and reactors your cells and that
things have to flow from one part of
your body to the next in a specific
composition to react now I would like us
all in this context to imagine for a
moment who are shrinking ourselves down
and we’re going to become a nanoparticle
we’re going to become 50 nanometers and
we are flowing in the bloodstream and
what we see we see those doughnut shape
big red blood cells and were bouncing of
them and we’re actually about hundred
times smaller than them it’s like a
human it’s staring at a six-story
building but we’re all flowing together
cells particles and other things in the
blood now at the same time we see in
front of us those small molecules that
are actually zigzagging at fast
velocities a small molecule now is about
100 times smaller than us the nano
particle so it’s like now the small
molecule is looking at the six story
building now a small molecule is moving
not because of the flow so much but
primarily because of its random motion
which is also called Brownian motion so
it’s a nanotechnologist when I look at
small molecules I call them little
lunatics because I have very little
control over where they go and this
brings us doesn’t bring us to anything
this brings us to actual cancer drugs
cancer drugs
are lethal toxic molecules that have
been selected based on their potency to
kill cancer cells in a petri dish so
when we inject them into cancer patients
we try to achieve sufficient
concentration and levels of the drug at
the tumor site and by doing that we have
to innovate the concentration of the
drugs throughout the entire body because
again we have very little control over
where those molecules go and this is the
battle in oncology kill the tumor before
you kill the patient
and that’s where nanotechnology came and
gave an answer or tried to give an
answer to this important problem and
that was the early success story of nano
medicine or nano medicine 20 or so years
ago nanoparticles exploit one of tumors
unique features called angiogenesis as
two most rat start growing they outgrow
the existing supply of nutrients and
oxygen so the quickly they start
building their own blood vessels and
those blood vessels are very imperfect
and immature and they have big gaps big
holes on their vessel walls compared to
the tight junctions that the walls of
normal blood vessels have so when we
packaged a cancer drug into a
nanoparticle when we inject it into the
bloodstream of a cancer patient the
nanoparticle cannot escape the normal
blood vessels in healthy tissues but
very efficiently can start squeezing
into those holes into tumors and
delivering drugs into concentrate into
cancer cells and this worked very very
well for many types of cancer
unfortunately does not work for some of
the most lethal cancers for example
brain tumors well know that brain 2 must
still remain a highly lethal disease and
there are quite a few reasons why brain
tumors
fade today’s therapies fail to treat
brain tumors first brain tumors like
glioblastoma multiforme exhibit the huge
growth with infiltrating edges
protruding into the normal tissue
this makes surgical
you’re nearly impossible at the same
time at the same time at the second time
is that the second problem is that the
blood-brain barrier protects the brain
from small molecules that circulate in
the bloodstream to gain access into the
brain normal tissue and last is that
brain tumors consists of cells
subpopulations with actual great
plasticity including cells that have
stem-like properties that are highly
resistant to chemotherapy and radiation
and these are these are the cells that
are responsible for the rapid recurrence
of the disease apologize for this so in
order to tackle this serious clinical
problem we actually use nanoparticles as
our building blocks we have come up with
an elegant way of taking any
nanoparticle and giving it to faces in
terms of chemical functionality which
now can be can be used as fittings to
start assembling one nanoparticle after
the other kind of like a stack of Legos
so it’s nanoparticle can be of different
function can be of different type while
the overall shape of this nano chain
particle gives the unique ability to
seek and target the site of disease more
specifically we will decorate the
surface of this nanoparticle with small
molecules called ligands that hi were
very specifically target biomarkers of
the disease on the walls of the blood
vessels in brain tumors it’s late
rather than targeting the brain tumor
cells themselves which are actually
sitting behind the blood-brain barrier
and deep inside the tissue we are
actually directing the nano chain
particle to go and park itself on the
vessel walls of the disease compared to
small molecules or spherical particles
then I’m not saying and it’s flexibility
has a unique overall ability to scavenge
for those biomarkers of the disease
while circulating the blood and lots
with great strength once it recognizes
those biomarkers all the vessels in
brain tumors so in essence we can
generate well-distributed reservoirs of
those drug carrying nanoparticles
throughout the entire tumor volume in
its primary site in its infiltrating
edges and also in established distant
invasive sites however the only thing we
have achieved so far is that we have
given lots of drug reservoirs throughout
the tumor volume but the drug has not
escaped the nanoparticle to gain access
into the tumor cells and that’s where
the different components of the Nano
chain come into play one of our most
successful designs is actually made of
three iron iron nanoparticles and one
lipid sac the lipid sac can be loaded
with different amounts of drug and it
can be loaded with different types of
track the iron oxide particles are
superparamagnetic they’re kind of kind
of like tiny little magnets which they
can respond to an alternating magnetic
field so using off-the-shelf audio
amplifiers and a low-power magnetic
field kind of like AM radio those
magnetic particles that make the Nano
chain in their effort to align to this
radio frequency field they start
vibrating and this vibration quickly
translates to a violent mechanical
vibration that
shakes the violently the lipid sag and
bursts on our command and that liberates
free drug which can now do what they can
do very well
the little lunatics now can spread
throughout the entire tumor so we’ll try
to illustrate this I will try to
illustrate this with images of brain
tissues using a microscope in green we
can see the brain tumor we can see it’s
infiltrating edges we can see the
migration and the establishment of a new
distant invasive site now if we take a
closer look we can actually see that we
have in red the blood vessels we can see
the cancer cells behind it and in blue
we can see those nano chain particles
that have talked themselves onto the
vessel walls of those blood vessels in
brain tumors so under the influence of a
mild radio frequency field the drug
actually escapes the Nano carriers and
like a tsunami spread throughout the
entire tumor volume and gains access to
it and every brain tumor cell so as new
contemporary drugs are continuously
becoming available not only for brain
tumors but also for neurodegenerative
diseases of the central nervous system
we work very closely with
neuroscientists and neurologists to make
impactful nanomedicines and break them
to the clinic thank you
[Applause]
you
my name is Stathis and I’m a biomedical
engineer and an associate professor here
at Case Western Reserve University so
today I’m going to talk to you about my
labs work on cancer nanotechnology and
our quest for the ultimate tract
smuggler so before I begin I have to
make a confession before I became a
biomedical engineer I was actually
trained as a chemical engineer in my
undergraduate schooling so when I look
at all of you I cannot help myself but
see a collection of pipes your blood
vessels and reactors your cells and that
things have to flow from one part of
your body to the next in a specific
composition to react now I would like us
all in this context to imagine for a
moment who are shrinking ourselves down
and we’re going to become a nanoparticle
we’re going to become 50 nanometers and
we are flowing in the bloodstream and
what we see we see those doughnut shape
big red blood cells and were bouncing of
them and we’re actually about hundred
times smaller than them it’s like a
human it’s staring at a six-story
building but we’re all flowing together
cells particles and other things in the
blood now at the same time we see in
front of us those small molecules that
are actually zigzagging at fast
velocities a small molecule now is about
100 times smaller than us the nano
particle so it’s like now the small
molecule is looking at the six story
building now a small molecule is moving
not because of the flow so much but
primarily because of its random motion
which is also called Brownian motion so
it’s a nanotechnologist when I look at
small molecules I call them little
lunatics because I have very little
control over where they go and this
brings us doesn’t bring us to anything
this brings us to actual cancer drugs
cancer drugs
are lethal toxic molecules that have
been selected based on their potency to
kill cancer cells in a petri dish so
when we inject them into cancer patients
we try to achieve sufficient
concentration and levels of the drug at
the tumor site and by doing that we have
to innovate the concentration of the
drugs throughout the entire body because
again we have very little control over
where those molecules go and this is the
battle in oncology kill the tumor before
you kill the patient
and that’s where nanotechnology came and
gave an answer or tried to give an
answer to this important problem and
that was the early success story of nano
medicine or nano medicine 20 or so years
ago nanoparticles exploit one of tumors
unique features called angiogenesis as
two most rat start growing they outgrow
the existing supply of nutrients and
oxygen so the quickly they start
building their own blood vessels and
those blood vessels are very imperfect
and immature and they have big gaps big
holes on their vessel walls compared to
the tight junctions that the walls of
normal blood vessels have so when we
packaged a cancer drug into a
nanoparticle when we inject it into the
bloodstream of a cancer patient the
nanoparticle cannot escape the normal
blood vessels in healthy tissues but
very efficiently can start squeezing
into those holes into tumors and
delivering drugs into concentrate into
cancer cells and this worked very very
well for many types of cancer
unfortunately does not work for some of
the most lethal cancers for example
brain tumors well know that brain 2 must
still remain a highly lethal disease and
there are quite a few reasons why brain
tumors
fade today’s therapies fail to treat
brain tumors first brain tumors like
glioblastoma multiforme exhibit the huge
growth with infiltrating edges
protruding into the normal tissue
this makes surgical
you’re nearly impossible at the same
time at the same time at the second time
is that the second problem is that the
blood-brain barrier protects the brain
from small molecules that circulate in
the bloodstream to gain access into the
brain normal tissue and last is that
brain tumors consists of cells
subpopulations with actual great
plasticity including cells that have
stem-like properties that are highly
resistant to chemotherapy and radiation
and these are these are the cells that
are responsible for the rapid recurrence
of the disease apologize for this so in
order to tackle this serious clinical
problem we actually use nanoparticles as
our building blocks we have come up with
an elegant way of taking any
nanoparticle and giving it to faces in
terms of chemical functionality which
now can be can be used as fittings to
start assembling one nanoparticle after
the other kind of like a stack of Legos
so it’s nanoparticle can be of different
function can be of different type while
the overall shape of this nano chain
particle gives the unique ability to
seek and target the site of disease more
specifically we will decorate the
surface of this nanoparticle with small
molecules called ligands that hi were
very specifically target biomarkers of
the disease on the walls of the blood
vessels in brain tumors it’s late
rather than targeting the brain tumor
cells themselves which are actually
sitting behind the blood-brain barrier
and deep inside the tissue we are
actually directing the nano chain
particle to go and park itself on the
vessel walls of the disease compared to
small molecules or spherical particles
then I’m not saying and it’s flexibility
has a unique overall ability to scavenge
for those biomarkers of the disease
while circulating the blood and lots
with great strength once it recognizes
those biomarkers all the vessels in
brain tumors so in essence we can
generate well-distributed reservoirs of
those drug carrying nanoparticles
throughout the entire tumor volume in
its primary site in its infiltrating
edges and also in established distant
invasive sites however the only thing we
have achieved so far is that we have
given lots of drug reservoirs throughout
the tumor volume but the drug has not
escaped the nanoparticle to gain access
into the tumor cells and that’s where
the different components of the Nano
chain come into play one of our most
successful designs is actually made of
three iron iron nanoparticles and one
lipid sac the lipid sac can be loaded
with different amounts of drug and it
can be loaded with different types of
track the iron oxide particles are
superparamagnetic they’re kind of kind
of like tiny little magnets which they
can respond to an alternating magnetic
field so using off-the-shelf audio
amplifiers and a low-power magnetic
field kind of like AM radio those
magnetic particles that make the Nano
chain in their effort to align to this
radio frequency field they start
vibrating and this vibration quickly
translates to a violent mechanical
vibration that
shakes the violently the lipid sag and
bursts on our command and that liberates
free drug which can now do what they can
do very well
the little lunatics now can spread
throughout the entire tumor so we’ll try
to illustrate this I will try to
illustrate this with images of brain
tissues using a microscope in green we
can see the brain tumor we can see it’s
infiltrating edges we can see the
migration and the establishment of a new
distant invasive site now if we take a
closer look we can actually see that we
have in red the blood vessels we can see
the cancer cells behind it and in blue
we can see those nano chain particles
that have talked themselves onto the
vessel walls of those blood vessels in
brain tumors so under the influence of a
mild radio frequency field the drug
actually escapes the Nano carriers and
like a tsunami spread throughout the
entire tumor volume and gains access to
it and every brain tumor cell so as new
contemporary drugs are continuously
becoming available not only for brain
tumors but also for neurodegenerative
diseases of the central nervous system
we work very closely with
neuroscientists and neurologists to make
impactful nanomedicines and break them
to the clinic thank you
[Applause]
you
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