ACS Applied Materials & Interfaces,
Journal Year:
2022,
Volume and Issue:
14(7), P. 8782 - 8792
Published: Feb. 9, 2022
Chemoimmunotherapy
can
synergistically
enhance
the
therapeutic
effects
and
decrease
side
by
a
combined
method.
However,
effective
targeted
codelivery
of
various
chemotherapeutic
agents
siRNAs
remains
challenging.
Although
nanomedicine-based
chemoimmunotherapy
has
shown
great
potential
in
cancer
treatment
recent
years,
further
effort
is
needed
to
simplify
nanocarrier
designs
maintain
their
functions.
Here,
we
report
simple
but
robust
multifunctional
liposomal
that
contains
pH-sensitive
liposome
(LP)
shell
dendritic
core
for
tumor-targeted
programmed
cell
death
ligand
1
(PD-L1)
siRNA
doxorubicin
(DOX)
(siPD-L1@PM/DOX/LPs).
siPD-L1@PM/DOX/LPs
had
suitable
particle
size
zeta
potential,
excellent
stability
serum,
drug
release
vitro.
They
exhibited
significant
proliferation
inhibition
compared
free
DOX
DOX-loaded
LPs
could
escape
endosomes,
effectively
into
cytoplasm
MCF-7
cells,
significantly
reduce
PD-L1
expression
on
tumor
cells.
In
vivo
imaging
confirmed
high
accumulation
at
site.
More
importantly,
with
siPD-L1@PM/LPs
or
alone,
were
more
inhibiting
growth
activating
cytotoxic
T
cells
vivo.
conclusion,
this
may
hold
promise
as
nanoplatform
improve
solid
tumors.
Acta Pharmaceutica Sinica B,
Journal Year:
2022,
Volume and Issue:
13(2), P. 819 - 833
Published: Sept. 25, 2022
Chemotherapy
is
an
important
adjuvant
treatment
of
glioma,
while
the
efficacy
far
from
satisfactory,
due
not
only
to
biological
barriers
blood‒brain
barrier
(BBB)
and
blood‒tumor
(BTB)
but
also
intrinsic
resistance
glioma
cells
via
multiple
survival
mechanisms
such
as
up-regulation
P-glycoprotein
(P-gp).
To
address
these
limitations,
we
report
a
bacteria-based
drug
delivery
strategy
for
BBB/BTB
transportation,
targeting,
chemo-sensitization.
Bacteria
selectively
colonized
into
hypoxic
tumor
region
modulated
microenvironment,
including
macrophages
repolarization
neutrophils
infiltration.
Specifically,
migration
was
employed
hitchhiking
doxorubicin
(DOX)-loaded
bacterial
outer
membrane
vesicles
(OMVs/DOX).
By
virtue
surface
pathogen-associated
molecular
patterns
derived
native
bacteria,
OMVs/DOX
could
be
recognized
by
neutrophils,
thus
facilitating
targeted
with
significantly
enhanced
accumulation
18-fold
compared
classical
passive
targeting
effect.
Moreover,
P-gp
expression
on
silenced
bacteria
type
III
secretion
effector
sensitize
DOX,
resulting
in
complete
eradication
100%
all
treated
mice.
In
addition,
were
finally
cleared
anti-bacterial
activity
DOX
minimize
potential
infection
risk,
cardiotoxicity
avoided,
achieving
excellent
compatibility.
This
work
provides
efficient
trans-BBB/BTB
cell
therapy.
Acta Pharmaceutica Sinica B,
Journal Year:
2023,
Volume and Issue:
13(5), P. 2176 - 2187
Published: Feb. 21, 2023
Intelligent
responsive
drug
delivery
system
opens
up
new
avenues
for
realizing
safer
and
more
effective
combination
immunotherapy.
Herein,
a
kind
of
tumor
cascade-targeted
liposome
(NLG919@Lip-pep1)
is
developed
by
conjugating
polypeptide
inhibitor
PD-1
signal
pathway
(AUNP-12),
which
also
targeted
peptide
that
conjugated
with
carrier
through
matrix
metalloproteinase-2
(MMP-2)
cleavable
(GPLGVRGD).
This
prepared
mature
preparation
process,
indoleamine-2,3-dioxygenase
(IDO)
NLG919
was
encapsulated
into
it.
Moreover,
mediated
the
enhanced
permeability
retention
effect
(EPR
effect)
AUNP-12,
NLG919@Lip-pep1
first
targets
cells
highly
express
PD-L1
in
tissues.
At
same
time,
over-expressed
MMP-2
site
triggers
dissociation
thus
precise
block
pathway,
restoring
activity
T
cells.
The
exposure
secondary
targeting
module
II
VRGDC-NLG919@Lip
targeting,
further
relieved
immunosuppressive
microenvironment.
Overall,
this
study
offers
potentially
appealing
paradigm
high
efficiency,
low
toxicity,
simple
intelligent
breast
cancer,
can
effectively
rescue
activate
body's
anti-tumor
immune
response
furthermore
achieve
treatment
metastatic
cancer.
Frontiers in Drug Delivery,
Journal Year:
2024,
Volume and Issue:
4
Published: March 12, 2024
The
delivery
of
therapeutics
into
the
brain
is
highly
limited
by
blood-brain
barrier
(BBB).
Although
this
essential
to
protect
from
potentially
harmful
material
found
in
blood,
it
poses
a
great
challenge
for
treatment
diseases
affecting
central
nervous
system
(CNS).
Substances
periphery
that
are
required
function
must
rely
on
active
mechanisms
entry.
One
such
physiological
pathway
called
receptor-mediated
transcytosis
(RMT).
In
process,
ligands
bind
specific
receptors
expressed
at
luminal
membrane
endothelial
cells
composing
BBB
leading
internalization
receptor-ligand
complex
intracellular
vesicles,
their
trafficking
through
various
compartments
and
finally
fusion
with
abluminal
release
cargo
brain.
Targeting
RMT
crossing
represents
an
emerging
clinically
validated
strategy
increase
permeability
biologicals.
However,
choice
appropriate
receptor
critical
achieve
best
selectivity
efficacy
method.
Whereas
majority
work
has
been
focused
transferrin
(Tf)
(TfR),
search
novel
(BECs)
can
deliver
protein
or
viral
vector
cargos
across
yielded
several
targets
diverse
molecular/structural
properties
biological
functions,
transcytosis.
review,
we
summarize
well-studied
pathways,
explore
engaged
transport
receptors.
We
then
discuss
key
criteria
would
be
desired
optimal
target,
based
lessons-learned
studies
TfR
accumulating
experimental
evidence
ligands.
Pharmaceutics,
Journal Year:
2021,
Volume and Issue:
13(12), P. 2024 - 2024
Published: Nov. 27, 2021
The
blood-brain
barrier
(BBB)
precisely
controls
brain
microenvironment
and
neural
activity
by
regulating
substance
transport
into
out
of
the
brain.
However,
it
severely
hinders
drug
entry
brain,
efficiency
various
systemic
therapies
against
diseases.
Modulation
BBB
via
opening
tight
junctions,
inhibiting
active
efflux
and/or
enhancing
transcytosis,
possesses
potential
to
increase
permeability
improve
intracranial
concentrations
therapeutic
efficiency.
Various
strategies
modulation
have
been
reported
investigated
preclinically
clinically.
This
review
describes
conventional
emerging
related
mechanisms,
safety
issues
according
structures
functions,
try
give
more
promising
directions
for
designing
reasonable
preclinical
clinical
studies.
Expert Opinion on Drug Delivery,
Journal Year:
2022,
Volume and Issue:
19(6), P. 685 - 705
Published: June 3, 2022
Introduction
Compared
to
normal
cells,
malignant
cancer
cells
require
more
iron
for
their
growth
and
rapid
proliferation,
which
can
be
supplied
by
a
high
expression
level
of
transferrin
receptor
(TfR).
It
is
well
known
that
the
TfR
on
tumor
considerably
higher
than
makes
an
attractive
target
in
therapy.Areas
covered
In
this
review,
primary
focus
role
as
valuable
tool
cancer-targeted
drug
delivery,
followed
full
coverage
available
ligands
conjugation
chemistry
surface
liposomes.
Finally,
most
recent
studies
investigating
potential
TfR-targeted
liposomes
promising
delivery
vehicles
different
are
highlighted
with
emphasis
improvement
possibilities
become
part
future
medicines.Expert
opinion
Liposomes
class
nanocarriers
have
gained
much
attention
toward
therapy.
From
all
exploited
therapeutic
diagnostic
it
realized
systematic
assessment
applied
liposomal
targeted
has
yet
entirely
accomplished.
Acta Pharmaceutica Sinica B,
Journal Year:
2022,
Volume and Issue:
13(1), P. 298 - 314
Published: May 29, 2022
Metastasis
accounts
for
90%
of
breast
cancer
deaths,
where
the
lethality
could
be
attributed
to
poor
drug
accumulation
at
metastatic
loci.
The
tolerance
chemotherapy
induced
by
stem
cells
(BCSCs)
and
their
particular
redox
microenvironment
further
aggravate
therapeutic
dilemma.
To
specific,
therapy-resistant
BCSCs
can
differentiate
into
heterogeneous
tumor
constantly,
simultaneously
dynamic
maintenance
homeostasis
promote
retro-differentiate
stem-like
state
in
response
cytotoxic
chemotherapy.
Herein,
we
develop
a
specifically-designed
biomimic
platform
employing
neutrophil
membrane
as
shell
inherit
neutrophil-like
tumor-targeting
capability,
anchored
chemotherapeutic
BCSCs-differentiating
reagents
with
nitroimidazole
(NI)
yield
two
hypoxia-responsive
prodrugs,
which
encapsulated
polymeric
core.
actively
target
lung
metastasis
sites
triple
negative
(TNBC),
release
escorted
drugs
upon
being
triggered
hypoxia
microenvironment.
During
responsiveness,
differentiating
agent
transferring
non-BCSCs,
moieties
conjugated
on
polymer
prodrugs
modulate
depleting
nicotinamide
adenine
dinucleotide
phosphate
hydrogen
(NADPH)
amplifying
intracellular
oxidative
stress
prevent
retro-differentiation
BCSCs.
In
combination,
differentiation
modulation
synergistically
enhance
cytotoxicity,
remarkably
suppress
growth
metastasis.
Hopefully,
this
work
provide
new
insight
comprehensively
treat
TNBC
using
versatile
platform.
Expert Opinion on Drug Delivery,
Journal Year:
2023,
Volume and Issue:
20(12), P. 1713 - 1730
Published: Aug. 5, 2023
A
major
challenge
in
treating
central
nervous
system
(CNS)
disorders
is
to
achieve
adequate
drug
delivery
across
the
blood-brain
barrier
(BBB).
Receptor-mediated
nanodrug
as
a
Trojan
horse
strategy
has
become
an
exciting
approach.
However,
these
nanodrugs
do
not
accumulate
significantly
brain
parenchyma,
which
greatly
limits
therapeutic
effect
of
drugs.
Amplifying
efficiency
receptor-mediated
BBB
becomes
holy
grail
treatment
CNS
disorders.