ACS Nano,
Год журнала:
2022,
Номер
16(6), С. 8729 - 8750
Опубликована: Май 26, 2022
Glioblastoma
(GBM)
is
an
aggressive
primary
brain
cancer,
with
a
5
year
survival
of
∼5%.
Challenges
that
hamper
GBM
therapeutic
efficacy
include
(i)
tumor
heterogeneity,
(ii)
treatment
resistance,
(iii)
immunosuppressive
microenvironment
(TME),
and
(iv)
the
blood-brain
barrier
(BBB).
The
C-X-C
motif
chemokine
ligand-12/C-X-C
receptor-4
(CXCL12/CXCR4)
signaling
pathway
activated
in
associated
progression.
Although
CXCR4
antagonist
(AMD3100)
has
been
proposed
as
attractive
anti-GBM
target,
it
poor
pharmacokinetic
properties,
unfavorable
bioavailability
hampered
its
clinical
implementation.
Thus,
we
developed
synthetic
protein
nanoparticles
(SPNPs)
coated
transcytotic
peptide
iRGD
(AMD3100-SPNPs)
to
target
CXCL2/CXCR4
via
systemic
delivery.
We
showed
AMD3100-SPNPs
block
CXCL12/CXCR4
three
mouse
human
cell
cultures
vitro
model
vivo.
This
results
inhibition
proliferation,
reduced
infiltration
CXCR4+
monocytic
myeloid-derived
suppressor
cells
(M-MDSCs)
into
TME,
restoration
BBB
integrity,
induction
immunogenic
death
(ICD),
sensitizing
radiotherapy
leading
immunity.
Additionally,
combining
radiation
led
long-term
survival,
∼60%
tumor-bearing
mice
remaining
free
after
rechallenging
second
contralateral
hemisphere.
was
due
sustained
immunological
memory
response
prevented
recurrence
without
additional
treatment.
In
view
potent
ICD
reprogrammed
microenvironment,
this
SPNP-mediated
strategy
significant
translation
applicability.
Journal of Controlled Release,
Год журнала:
2016,
Номер
235, С. 34 - 47
Опубликована: Май 19, 2016
The
blood-brain
barrier
(BBB)
is
a
vital
boundary
between
neural
tissue
and
circulating
blood.
BBB's
unique
protective
features
control
brain
homeostasis
as
well
ion
molecule
movement.
Failure
in
maintaining
any
of
these
components
results
the
breakdown
this
specialized
multicellular
structure
consequently
promotes
neuroinflammation
neurodegeneration.
In
several
high
incidence
pathologies
such
stroke,
Alzheimer's
(AD)
Parkinson's
disease
(PD)
BBB
impaired.
However,
even
damaged
more
permeable
can
pose
serious
challenges
to
drug
delivery
into
brain.
use
nanoparticle
(NP)
formulations
able
encapsulate
molecules
with
therapeutic
value,
while
targeting
specific
transport
processes
vasculature,
may
enhance
through
neurodegenerative/ischemic
disorders
target
relevant
regions
for
regenerative
processes.
review,
we
will
discuss
composition
characteristics
how
are
altered
pathology,
namely
AD
PD.
Additionally,
factors
influencing
an
efficient
intravenous
polymeric
inorganic
NPs
NP-related
systems
most
promising
functional
outcomes
also
be
discussed.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Дек. 20, 2019
Abstract
Microglia
survey
brain
parenchyma,
responding
to
injury
and
infections.
also
respond
systemic
disease,
but
the
role
of
blood–brain
barrier
(BBB)
integrity
in
this
process
remains
unclear.
Using
simultaneous
vivo
imaging,
we
demonstrated
that
inflammation
induces
CCR5-dependent
migration
resident
microglia
cerebral
vasculature.
Vessel-associated
initially
maintain
BBB
via
expression
tight-junction
protein
Claudin-5
make
physical
contact
with
endothelial
cells.
During
sustained
inflammation,
phagocytose
astrocytic
end-feet
impair
function.
Our
results
show
play
a
dual
maintaining
implications
for
elucidating
how
immune-activation
impacts
neural
functions.
Annals of Neurology,
Год журнала:
2012,
Номер
72(5), С. 648 - 672
Опубликована: Май 22, 2012
The
blood-brain
barrier
(BBB)
is
a
term
used
to
describe
series
of
properties
possessed
by
the
vasculature
central
nervous
system
(CNS)
that
tightly
regulate
movement
ions,
molecules,
and
cells
between
blood
CNS.
This
crucial
provide
appropriate
environment
allow
for
proper
neural
function,
as
well
protect
CNS
from
injury
disease.
In
this
review,
I
discuss
cellular
molecular
composition
BBB
how
development
function
regulated
interactions
with
microenvironment.
further
what
known
about
dysfunction
during
disease,
methodology
deliver
drugs
across
Fluids and Barriers of the CNS,
Год журнала:
2012,
Номер
9(1)
Опубликована: Ноя. 9, 2012
Abstract
The
Blood–brain
barrier
(BBB),
present
at
the
level
of
endothelium
cerebral
blood
vessels,
selectively
restricts
blood-to-brain
paracellular
diffusion
compounds;
it
is
mandatory
for
homeostasis
and
proper
neuronal
function.
properties
these
specialized
endothelial
cells
notably
depend
on
tight
junctions
(TJs)
between
adjacent
cells:
TJs
are
dynamic
structures
consisting
a
number
transmembrane
membrane-associated
cytoplasmic
proteins,
which
assembled
in
multimolecular
complex
acting
as
platform
intracellular
signaling.
Although
structural
composition
complexes
has
been
well
described
recent
years,
our
knowledge
about
their
functional
regulation
still
remains
fragmentary.
Importantly,
pericytes,
embedded
vascular
basement
membrane,
perivascular
microglial
cells,
astrocytes
neurons
contribute
to
BBB
function,
altogether
constituting
so-called
neurovascular
unit.
review
summarizes
current
understanding
structure
BBB.
Accumulating
evidence
points
correlation
dysfunction,
alteration
TJ
progression
variety
CNS
diseases,
such
stroke,
multiple
sclerosis
brain
tumors,
neurodegenerative
diseases
like
Parkinson’s
Alzheimer’s
diseases.
Understanding
how
integrity
controlled
may
thus
help
improve
drug
delivery
across
design
therapeutic
strategies
neurological
disorders.
Frontiers in Cellular Neuroscience,
Год журнала:
2014,
Номер
8
Опубликована: Ноя. 3, 2014
The
blood-brain
barrier
(BBB),
constituted
by
an
extensive
network
of
endothelial
cells
together
with
neurons
and
glial
cells,
including
microglia,
forms
the
neurovascular
unit.
crosstalk
between
these
guarantees
a
proper
environment
for
brain
function.
In
this
context,
changes
in
endothelium-microglia
interactions
are
associated
variety
inflammation-related
diseases
brain,
where
BBB
permeability
is
compromised.
Increasing
evidences
indicate
that
activated
microglia
modulate
expression
tight
junctions,
which
essential
integrity
On
other
hand,
endothelium
can
regulate
state
microglial
activation.
Here,
we
review
recent
advances
provide
insights
into
vascular
system
such
as
infectious/inflammatory
diseases,
epilepsy,
ischemic
stroke
neurodegenerative
disorders.
AJP Cell Physiology,
Год журнала:
2018,
Номер
315(3), С. C343 - C356
Опубликована: Июнь 27, 2018
The
blood-brain
barrier
(BBB)
is
a
physical
and
biochemical
that
precisely
controls
cerebral
homeostasis.
It
also
plays
central
role
in
the
regulation
of
blood-to-brain
flux
endogenous
exogenous
xenobiotics
associated
metabolites.
This
accomplished
by
molecular
characteristics
brain
microvessel
endothelial
cells
such
as
tight
junction
protein
complexes
functional
expression
influx
efflux
transporters.
One
pathophysiological
features
ischemic
stroke
disruption
BBB,
which
significantly
contributes
to
development
injury
subsequent
neurological
impairment.
Biochemical
BBB
damage
include
decreased
altered
organization
constituent
proteins
well
modulation
Therefore,
there
critical
need
for
novel
therapeutic
strategies
can
protect
against
dysfunction
(i.e.,
vascular
protection)
setting
stroke.
Such
targeting
junctions
ensure
they
maintain
their
correct
structure
or
transporters
control
physiological
substrates
protection
In
this
review,
we
will
describe
mechanisms
microvascular
lead
following
onset
Additionally,
utilize
state-of-the-art
knowledge
provide
insights
on
pharmacological
be
developed
confer
