Reprogramming
the
immunosuppressive
tumor
microenvironment
by
modulating
macrophages
holds
great
promise
in
immunotherapy.
As
a
class
of
professional
phagocytes
and
antigen-presenting
cells
innate
immune
system,
can
not
only
directly
engulf
clear
cells,
but
also
play
roles
presenting
tumor-specific
antigen
to
initiate
adaptive
immunity.
However,
tumor-associated
(TAMs)
usually
display
tumor-supportive
M2
phenotype
rather
than
anti-tumor
M1
phenotype.
They
support
escape
immunological
surveillance,
aggravate
progression,
impede
T
cell
Although
many
TAMs-modulating
agents
have
shown
success
therapy
multiple
tumors,
they
face
enormous
challenges
including
poor
accumulation
off-target
side
effects.
An
alternative
solution
is
use
advanced
nanostructures,
which
deliver
augment
therapeutic
efficacy,
serve
as
modulators
TAMs.
Another
important
strategy
exploitation
macrophage-derived
components
tumor-targeting
delivery
vehicles.
Herein,
we
summarize
recent
advances
targeting
engineering
for
immunotherapy,
(1)
direct
indirect
effects
on
augmentation
immunotherapy
(2)
strategies
macrophage-based
drug
carriers.
The
existing
perspectives
immunotherapies
are
highlighted.
Theranostics,
Год журнала:
2021,
Номер
11(11), С. 5365 - 5386
Опубликована: Янв. 1, 2021
Immunotherapy,
represented
by
immune
checkpoint
inhibitors
(ICIs),
has
greatly
improved
the
clinical
efficacy
of
malignant
tumor
therapy.
ICI-mediated
antitumor
responses
depend
on
infiltration
T
cells
capable
recognizing
and
killing
cells.
ICIs
are
not
effective
in
"cold
tumors",
which
characterized
lack
T-cell
infiltration.
To
realize
full
potential
immunotherapy
solve
this
obstacle,
it
is
essential
to
understand
drivers
into
tumors.
We
present
a
critical
review
our
understanding
mechanisms
underlying
including
impaired
priming
deficient
homing
beds.
"Hot
tumors"
with
significant
associated
better
ICI
efficacy.
In
review,
we
summarize
multiple
strategies
that
promote
transformation
"hot
discuss
these
lead
increased
Finally,
application
nanomaterials
provide
an
outlook
future
emerging
field.
The
combination
nanomedicines
enhances
cross-presentation
antigens
promotes
A
deeper
opens
new
possibilities
for
development
cell-based
therapies
improve
effectiveness.
Theranostics,
Год журнала:
2020,
Номер
10(10), С. 4557 - 4588
Опубликована: Янв. 1, 2020
In
recent
years,
much
progress
has
been
motivated
in
stimuli-responsive
nanocarriers,
which
could
response
to
the
intrinsic
physicochemical
and
pathological
factors
diseased
regions
increase
specificity
of
drug
delivery.
Currently,
numerous
nanocarriers
have
engineered
with
changes
responding
external
stimuli,
such
as
ultrasound,
thermal,
light
magnetic
field,
well
internal
including
pH,
redox
potential,
hypoxia
enzyme,
etc.
Nanocarriers
respond
stimuli
tumor
microenvironments
or
inside
cancer
cells
for
on-demanded
delivery
accumulation,
controlled
release,
activation
bioactive
compounds,
probes
targeting
ligands,
size,
charge
conformation
conversion,
etc.,
leading
sensing
signaling,
overcoming
multidrug
resistance,
accurate
diagnosis
precision
therapy.
This
review
summarized
general
strategies
developing
advances,
presented
their
applications
delivery,
imaging,
therapy
theranostics,
illustrated
clinical
translation
made
prospects.
Advanced Materials,
Год журнала:
2020,
Номер
32(47)
Опубликована: Окт. 16, 2020
Ultrasound
(US)-triggered
sonodynamic
therapy
(SDT),
as
a
promising
noninvasive
therapeutic
modality,
has
received
ever-increasing
attention
in
recent
years.
Its
specialized
chemical
agents,
named
sonosensitizers,
are
activated
by
low-intensity
US
to
produce
lethal
reactive
oxygen
species
(ROS)
for
oncotherapy.
Compared
with
phototherapeutic
strategies,
SDT
provides
many
noteworthy
opportunities
and
benefits,
such
deeper
penetration
depth,
absence
of
phototoxicity,
fewer
side
effects.
Nevertheless,
previous
studies
have
also
demonstrated
its
intrinsic
limitations.
Thanks
the
facile
engineering
nature
nanotechnology,
numerous
novel
nanoplatforms
being
applied
this
emerging
field
tackle
these
barriers
achieve
continuous
innovations.
In
particular,
combination
other
treatment
strategies
superior
efficacy
improving
anticancer
activity
relative
that
monotherapies
alone.
Therefore,
it
is
necessary
summarize
nanomaterial-assisted
combinational
cancer
applications.
Herein,
design
principles
achieving
synergistic
effects
based
on
nanomaterial
methods
highlighted.
The
ultimate
goals
stimulate
better-quality
combined
schemes
provide
innovative
ideas
perspectives
promoting
future
transformation
clinical
application.
Abstract
Tumor
immunotherapy
is
only
effective
in
a
fraction
of
patients
due
to
low
response
rate
and
severe
side
effects,
these
challenges
clinics
can
be
addressed
through
induction
immunogenic
cell
death
(ICD).
ICD
elicited
from
many
antitumor
therapies
release
danger
associated
molecular
patterns
(DAMPs)
tumor‐associated
antigens
facilitate
maturation
dendritic
cells
(DCs)
infiltration
cytotoxic
T
lymphocytes
(CTLs).
The
process
reverse
the
tumor
immunosuppressive
microenvironment
improve
sensitivity
immunotherapy.
Nanostructure‐based
drug
delivery
systems
(NDDSs)
are
explored
induce
by
incorporating
therapeutic
molecules
for
chemotherapy,
photosensitizers
(PSs)
photodynamic
therapy
(PDT),
photothermal
conversion
agents
(PTT),
radiosensitizers
radiotherapy
(RT).
These
NDDSs
loaded
at
right
dose
place
time,
resulting
greater
effectiveness
lower
toxicity.
Immunotherapeutic
also
combined
with
achieve
synergic
effect
multi‐modality
approach.
In
this
review,
harnessed
load
multiple
PDT,
PTT,
RT
combination
promote
reduce
effects
cancer
treatment.
Advanced Materials,
Год журнала:
2020,
Номер
33(4)
Опубликована: Дек. 2, 2020
Abstract
The
past
decades
have
witnessed
hyperthermia
therapy
(HTT)
as
an
emerging
strategy
against
malignant
tumors.
Nanomaterial‐based
photothermal
(PTT)
and
magnetic
(MHT),
highly
effective
noninvasive
treatment
models,
offer
advantages
over
other
strategies
in
the
of
different
types
However,
both
PTT
MHT
cannot
completely
cure
cancer
due
to
recurrence
distal
metastasis.
In
recent
years,
immunotherapy
has
attracted
widespread
attention
owing
its
capability
activate
body's
own
natural
defense
identify,
attack,
eradicate
cells.
Significant
efforts
been
devoted
studying
activated
immune
responses
caused
by
hyperthermia‐ablated
this
article,
synergistic
mechanism
HTT
immunotherapy,
including
immunogenic
cell
death
reversal
immunosuppressive
tumor
microenvironment
is
discussed.
reports
combination
or
HTT‐based
multimodal
with
immunoadjuvant
exploitation,
checkpoint
blockade
therapy,
adoptive
cellular
are
summarized.
As
highlighted,
these
could
achieve
synergistically
enhanced
therapeutic
outcomes
primary
tumors
metastatic
lesions,
prevent
recurrence,
prolong
survival
period.
Finally,
current
challenges
prospective
developments
HTT‐synergized
also
reviewed.
Angewandte Chemie International Edition,
Год журнала:
2019,
Номер
59(21), С. 7990 - 8003
Опубликована: Дек. 4, 2019
The
direct
difunctionalization
of
alkenes,
a
cheap
and
abundant
feedstock,
represents
one
the
most
attractive
strategies
for
increasing
molecular
complexity
in
synthetic
organic
chemistry.
In
contrast
with
1,2-difunctionalization
recent
advances
showcase
alkene
1,n-difunctionalizations
(n≠2)
involving
metal
migration
is
an
emerging
rapidly
growing
area
research.
This
promising
strategy
not
only
opens
novel
avenue
future
development
transformations,
but
also
significantly
expands
upon
bond
disconnections
available
modern
synthesis.
Minireview
summarizes
progress
migratory
emphasis
on
driving
force
migration.
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
Advanced Materials,
Год журнала:
2020,
Номер
33(4)
Опубликована: Дек. 16, 2020
Abstract
Immunotherapy
has
offered
new
treatment
options
for
cancer;
however,
the
therapeutic
benefits
are
often
modest
and
desired
to
be
improved.
A
semiconducting
polymer
nanoadjuvant
(SPN
II
R)
with
a
photothermally
triggered
cargo
release
second
near‐infrared
(NIR‐II)
photothermal
immunotherapy
is
reported
here.
SPN
R
consists
of
nanoparticle
core
as
an
NIR‐II
converter,
which
doped
toll‐like
receptor
(TLR)
agonist
adjuvant
coated
thermally
responsive
lipid
shell.
Upon
photoirradiation,
effectively
generates
heat
not
only
ablate
tumors
induce
immunogenic
cell
death
(ICD),
but
also
melt
layers
on‐demand
TLR
agonist.
The
combination
ICD
activation
TLR7/TLR8
enhances
maturation
dendritic
cells,
amplifies
anti‐tumor
immune
responses.
Thus,
single
R‐mediated
inhibits
growth
both
primary
distant
eliminates
lung
metastasis
in
murine
mouse
model.
This
study
thus
provides
remote‐controlled
smart
delivery
system
synergize
photomedicine
enhanced
cancer
treatment.
Angewandte Chemie International Edition,
Год журнала:
2019,
Номер
58(48), С. 17425 - 17432
Опубликована: Сен. 25, 2019
Abstract
Current
cancer
therapy
is
seriously
challenged
by
tumor
metastasis
and
recurrence.
One
promising
solution
to
these
problems
build
antitumor
immunity.
However,
immunotherapeutic
efficacy
highly
impeded
the
immunosuppressive
state
of
tumors.
Here
a
new
strategy
presented,
catalytic
immunotherapy
based
on
artificial
enzymes.
Cu
2−
x
Te
nanoparticles
exhibit
tunable
enzyme‐mimicking
activity
(including
glutathione
oxidase
peroxidase)
under
near‐infrared‐II
(NIR‐II)
light.
The
cascade
reactions
catalyzed
enzyme
gradually
elevates
intratumor
oxidative
stress
induce
immunogenic
cell
death.
Meanwhile,
continuously
generated
reverses
microenvironment,
boosts
immune
responses
eradicate
both
primary
distant
metastatic
Moreover,
immunological
memory
effect
successfully
acquired
after
treatment
with
suppress
relapse.
ACS Nano,
Год журнала:
2020,
Номер
14(12), С. 17442 - 17457
Опубликована: Ноя. 9, 2020
Nanomedicine,
acting
as
the
magic
bullet,
is
capable
of
combining
immunotherapy
with
other
treatments
to
reverse
a
cold
tumor
(immune
depletion)
into
hot
tumor.
However,
how
comprehensively
inhibit
immunosuppressive
microenvironment
(TME)
remains
major
challenge
for
achieve
maximum
benefits.
Thus,
strategy
that
can
simultaneously
increase
recruitment
infiltrating
lymphocytes
(TILs)
and
reprogram
TME
still
urgently
needed.
Herein,
thermal-sensitive
nitric
oxide
(NO)
donor
S-nitrosothiols
(SNO)-pendant
copolymer
(poly(acrylamide-co-acrylonitrile-co-vinylimidazole)-SNO
copolymer,
PAAV-SNO)
upper
critical
solution
temperature
(UCST)
was
synthesized
employed
fabricate
an
erythrocyte
membrane-camouflaged
nanobullet
codelivery
NIR
II
photothermal
agent
IR1061
indoleamine
2,3-dioxygenase
1
(IDO-1)
inhibitor
1-methyl-tryptophan
(1-MT).
This
multifunctional
possessed
long
circulation
in
vivo,
enhanced
accumulation
at
site,
therapeutics-controlled
release
by
laser,
thereby
it
could
avoid
unspecific
drug
leakage
while
enhancing
biosecurity.
More
importantly,
immunogenic
cell
death
(ICD)
induced
local
hyperthermia
from
therapy
(PTT)
be
conducive
increased
CD8+
cytotoxic
T
(CTLs)
site.
Furthermore,
through
interfering
IDO-1
activity
1-MT
normalizing
vessels
situ
generated
NO,
reprogrammed
toward
immunostimulatory
phenotype,
achieving
excellent
therapeutic
efficacy
against
both
primary
breast
cancer
metastases.
Collectively,
this
described
study
developed
effective
promising
suppressive
treat
"immune
cold"
tumors.