Frontiers in Pharmacology,
Год журнала:
2022,
Номер
12
Опубликована: Янв. 25, 2022
Cancer
is
a
life-threatening
disease,
contributing
approximately
9.4
million
deaths
worldwide.
To
address
this
challenge,
scientific
researchers
have
investigated
molecules
that
could
act
as
speed-breakers
for
cancer.
As
an
abiotic
drug
delivery
system,
liposomes
can
hold
both
hydrophilic
and
lipophilic
drugs,
which
promote
controlled
release,
accumulate
in
the
tumor
microenvironment,
achieve
elongated
half-life
with
enhanced
safety
profile.
further
improve
impair
off-target
effect,
surface
of
be
modified
way
easily
identified
by
cancer
cells,
promotes
uptake,
facilitates
angiogenesis.
Integrins
are
overexpressed
on
upon
activation
downstream
cell
signaling
eventually
activate
specific
pathways,
promoting
growth,
proliferation,
migration.
RGD
peptides
recognized
integrin
over
expressed
cells.
Just
like
multistage
rocket,
ligand
anchored
selectively
target
at
site,
finally,
release
desired
way.
This
review
highlights
role
development,
so
gain
more
insights
into
phenomenon
initiation
survival.
Since
family,
fate
has
been
demonstrated
after
its
binding
acceptor’s
family.
The
based
targeting
various
cells
also
highlighted
paper.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Май 25, 2023
Abstract
Blood–brain
barrier
(BBB)
is
a
natural
protective
membrane
that
prevents
central
nervous
system
(CNS)
from
toxins
and
pathogens
in
blood.
However,
the
presence
of
BBB
complicates
pharmacotherapy
for
CNS
disorders
as
most
chemical
drugs
biopharmaceuticals
have
been
impeded
to
enter
brain.
Insufficient
drug
delivery
into
brain
leads
low
therapeutic
efficacy
well
aggravated
side
effects
due
accumulation
other
organs
tissues.
Recent
breakthrough
materials
science
nanotechnology
provides
library
advanced
with
customized
structure
property
serving
powerful
toolkit
targeted
delivery.
In-depth
research
field
anatomical
pathological
study
on
further
facilitates
development
brain-targeted
strategies
enhanced
crossing.
In
this
review,
physiological
different
cells
contributing
are
summarized.
Various
emerging
permeability
regulation
crossing
including
passive
transcytosis,
intranasal
administration,
ligands
conjugation,
coating,
stimuli-triggered
disruption,
overcome
obstacle
highlighted.
Versatile
systems
ranging
organic,
inorganic,
biologics-derived
their
synthesis
procedures
unique
physio-chemical
properties
summarized
analyzed.
This
review
aims
provide
an
up-to-date
comprehensive
guideline
researchers
diverse
fields,
offering
perspectives
system.
Abstract
The
past
decades
have
witnessed
great
progress
in
cancer
immunotherapy,
which
has
profoundly
revolutionized
oncology,
whereas
low
patient
response
rates
and
potential
immune‐related
adverse
events
remain
major
clinical
challenges.
With
the
advantages
of
controlled
delivery
modular
flexibility,
nanomedicine
offered
opportunities
to
strengthen
antitumor
immune
responses
sensitize
tumor
immunotherapy.
Furthermore,
tumor‐microenvironment
(TME)‐responsive
been
demonstrated
achieve
specific
localized
amplification
tissue
a
safe
effective
manner,
increasing
immunotherapy
reducing
side
effects
simultaneously.
Here,
recent
TME‐responsive
for
is
summarized,
responds
signals
TME,
such
as
weak
acidity,
reductive
environment,
high‐level
reactive
oxygen
species,
hypoxia,
overexpressed
enzymes,
adenosine
triphosphate.
Moreover,
combine
nanomedicine‐based
therapy
immunotherapeutic
strategies
overcome
each
step
cancer‐immunity
cycle
enhance
discussed.
Finally,
existing
challenges
further
perspectives
this
rising
field
with
hope
improved
development
applications
are
Abstract
The
past
decades
have
witnessed
great
progress
in
nanoparticle
(NP)‐based
brain‐targeting
drug
delivery
systems,
while
their
therapeutic
potentials
are
yet
to
be
fully
exploited
given
that
the
majority
of
them
lost
during
process.
Rational
design
systems
requires
a
deep
understanding
entire
process
along
with
issues
they
may
encounter.
Herein,
this
review
first
analyzes
typical
systemically
administrated
NPs‐based
system
and
proposes
six‐step
CRITID
cascade:
circulation
systemic
blood,
recognizing
receptor
on
blood‐brain
barrier
(BBB),
intracellular
transport,
diseased
cell
targeting
after
entering
into
parenchyma,
internalization
by
cells,
finally
release.
By
dissecting
six
steps,
seeks
provide
restrict
efficiency
as
well
specific
requirements
guarantee
minimal
loss
at
each
step.
Currently
developed
strategies
used
for
troubleshooting
these
reviewed
some
state‐of‐the‐art
features
meeting
highlighted.
cascade
can
serve
guideline
designing
more
efficient
systems.
Glioblastoma
(GBM)
is
a
central
nervous
system
tumor
with
poor
prognosis
due
to
the
rapid
development
of
resistance
mono
chemotherapy
and
brain
targeted
delivery.
Chemoimmunotherapy
(CIT)
combines
drugs
activators
innate
immunity
that
hold
great
promise
for
GBM
synergistic
therapy.
Herein,
we
chose
temozolomide,
TMZ,
epigenetic
bromodomain
inhibitor,
OTX015,
further
co-encapsulated
them
within
our
well-established
erythrocyte
membrane
camouflaged
nanoparticle
yield
ApoE
peptide
decorated
biomimetic
nanomedicine
(ABNM@TMZ/OTX).
Our
nanoplatform
successfully
addressed
limitations
in
brain-targeted
drug
co-delivery,
simultaneously
achieved
multidimensional
enhanced
CIT.
In
mice
bearing
orthotopic
GL261
GBM,
treatment
ABNM@TMZ/OTX
resulted
marked
inhibition
greatly
extended
survival
time
little
side
effects.
The
pronounced
efficacy
can
be
ascribed
three
key
factors:
(i)
improved
nanoparticle-mediated
targeting
delivery
therapeutic
agents
by
blood
circulation
blood-brain
barrier
penetration;
(ii)
inhibited
cellular
DNA
repair
TMZ
sensitivity
cells;
(iii)
anti-tumor
immune
responses
inducing
immunogenic
cell
death
inhibiting
PD-1/PD-L1
conjugation
leading
expression
CD4
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 28, 2023
Abstract
Glioblastoma
(GBM)
remains
the
most
lethal
malignant
tumours.
Gboxin,
an
oxidative
phosphorylation
inhibitor,
specifically
restrains
GBM
growth
by
inhibiting
activity
of
F
0
1
ATPase
complex
V.
However,
its
anti-GBM
effect
is
seriously
limited
poor
blood
circulation,
brain
barrier
(BBB)
and
non-specific
tissue/cell
uptake,
leading
to
insufficient
Gboxin
accumulation
at
sites,
which
limits
further
clinical
application.
Here
we
present
a
biomimetic
nanomedicine
(HM-NPs@G)
coating
cancer
cell-mitochondria
hybrid
membrane
(HM)
on
surface
Gboxin-loaded
nanoparticles.
An
additional
design
element
uses
reactive
oxygen
species
responsive
polymer
facilitate
at-site
release.
The
HM
camouflaging
endows
HM-NPs@G
with
unique
features
including
good
biocompatibility,
improved
pharmacokinetic
profile,
efficient
BBB
permeability
homotypic
dual
tumour
cell
mitochondria
targeting.
results
suggest
that
achieve
circulation
(4.90
h
versus
0.47
free
Gboxin)
(7.73%
ID/g
1.06%
shown
Gboxin).
Effective
inhibition
in
orthotopic
U87MG
patient
derived
X01
stem
xenografts
female
mice
extended
survival
time
negligible
side
effects
are
also
noted.
We
believe
represents
promising
treatment
for
tumours
potential.
Biomaterials Research,
Год журнала:
2022,
Номер
26(1)
Опубликована: Июль 6, 2022
Theranostic
nanoplatforms
integrating
diagnostic
and
therapeutic
functions
have
received
considerable
attention
in
the
past
decade.
Among
them,
hollow
manganese
(Mn)-based
are
superior
since
they
combine
advantages
of
structures
intrinsic
theranostic
features
Mn
Colloids and Surfaces B Biointerfaces,
Год журнала:
2022,
Номер
221, С. 112999 - 112999
Опубликована: Ноя. 2, 2022
The
blood-brain
barrier
(BBB)
restricts
the
access
of
therapeutic
agents
to
brain,
complicating
treatment
neurological
diseases,
such
as
Alzheimer's
disease
(AD),
Parkinson's
(PD),
multiple
sclerosis
(MS),
glioma,
etc.
To
overcome
this
limitation
and
improve
drug
delivery
central
nervous
system
(CNS),
potential
nanocarriers,
including
lipid-based
nanosystems,
has
been
explored.
Through
active
targeting,
surface
nanocarriers
can
be
modified
with
ligands
that
interact
BBB,
enhancing
their
uptake
penetration
across
brain
endothelium
by
different
physiological
mechanisms,
receptor-
or
transporter-mediated
transcytosis.
This
review
seeks
provide
an
overview
targeting
in
delivery,
while
highlighting
functionalized
lipid
treat
diseases.
Therefore,
first
sections,
we
discuss
importance
CNS
present
commonly
used
for
functionalization,
well
summarize
state
art
most
recent
relevant
studies
surface-modified
nanosystems
developed
disorders.
Lastly,
challenges
hindering
clinical
translation
are
discussed,
critical
insights
future
perspectives
outlined.
Although
some
limitations
have
identified,
it
is
expected
upcoming
years
these
will
established
approach.
Abstract
Alzheimer's
disease
(AD),
as
a
progressive
and
irreversible
brain
disorder,
remains
the
most
universal
neurodegenerative
disease.
No
effective
therapeutic
methods
are
established
yet
due
to
hindrance
of
blood‐brain
barrier
(BBB)
complex
pathological
condition
AD.
Therefore,
multifunctional
nanocarrier
(Rapa@DAK/siRNA)
for
AD
treatment
is
constructed
achieve
small
interfering
RNA
β‐site
precursor
protein
(APP)
cleaving
enzyme‐1
(BACE1
siRNA)
rapamycin
co‐delivery
into
brain,
based
on
Aleuria
aurantia
lectin
(AAL)
β‐amyploid
(Aβ)‐binding
peptides
(KLVFF)
modified
PEGylated
dendrigraft
poly‐
l
‐lysines
(DGLs)
via
intranasal
administration.
Nasal
administration
provides
an
way
deliver
drugs
directly
through
nose‐to‐brain
pathway.
AAL,
specifically
binding
L‐fucose
located
in
olfactory
epithelium,
endows
Rapa@DAK/siRNA
with
high
entry
efficiency
KLVFF
peptide
Aβ
targeting
ligand
aggregation
inhibitor
enables
nanoparticles
bind
Aβ,
inhibit
aggregation,
reduce
toxicity.
Meanwhile,
release
BACE1
siRNA
confirmed
expression,
promote
autophagy,
deposition.
verified
improve
cognition
transgenic
mice
after
Collectively,
potential
avenue
combination
therapy
