Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(18), С. 13072 - 13085
Опубликована: Сен. 13, 2023
To
develop
next-generation
metal
drugs
with
high
efficiency
and
low
toxicity
for
targeting
inhibition
of
gastric
tumor
growth
metastasis,
we
not
only
optimized
a
series
ruthenium
(Ru,
III)
2-hydroxy-1-naphthaldehyde
thiosemicarbazone
complexes
to
obtain
Ru(III)
complex
(4b)
remarkable
cytotoxicity
in
vitro
but
also
constructed
4b-decitabine
(DCT)/liposome
(Lip)
delivery
system
(4b-DCT-Lip).
The
vivo
results
showed
that
4b-DCT-Lip
had
stronger
capacity
inhibit
metastasis
than
4b-DCT
addressed
the
co-delivery
problems
improved
their
ability.
Furthermore,
confirmed
mechanism
4b-DCT/4b-DCT-Lip
inhibiting
tumor.
DCT-upregulated
gasdermin
E
(GSDME)
was
cleaved
by
4b-activated
caspase-3
afford
GSDME-N
terminal
then
aggregated
form
nonselective
pores
on
cell
membrane
tumor,
thereby
inducing
pyroptosis
pyroptosis-induced
immune
response.
International Journal of Oral Science,
Год журнала:
2024,
Номер
16(1)
Опубликована: Март 13, 2024
Abstract
Despite
decades
of
research,
cancer
continues
to
be
a
major
global
health
concern.
The
human
mouth
appears
multiplicity
local
environments
communicating
with
other
organs
and
causing
diseases
via
microbes.
Nowadays,
the
role
oral
microbes
in
development
progression
has
received
increasing
scrutiny.
At
same
time,
bioengineering
technology
nanotechnology
is
growing
rapidly,
which
physiological
activities
natural
bacteria
are
modified
improve
therapeutic
efficiency
cancers.
These
engineered
were
transformed
achieve
directed
genetic
reprogramming,
selective
functional
reorganization
precise
control.
In
contrast
endotoxins
produced
by
typical
genetically
bacteria,
flora
exhibits
favorable
biosafety
characteristics.
To
outline
current
cognitions
upon
microbes,
cancers,
related
literatures
searched
reviewed
based
on
PubMed
database.
We
focused
number
mechanisms
associated
tumor
microenvironment,
involve
occurrence
development.
Whether
engineering
can
possible
application
therapy
worth
consideration.
A
deeper
understanding
relationship
between
may
enhance
our
knowledge
pathogenesis
thus
providing
new
insights
strategies
for
prevention
treatment.
Despite
significant
progress
in
cancer
treatment,
traditional
therapies
still
face
considerable
challenges,
including
poor
targeting,
severe
toxic
side
effects,
and
the
development
of
resistance.
Recent
advances
biotechnology
have
revealed
potential
bacteria
their
derivatives
as
drug
delivery
systems
for
tumor
therapy
by
leveraging
biological
properties.
Engineered
bacteria,
Escherichia
coli,
Salmonella,
Listeria
monocytogenes,
along
with
derivatives─outer
membrane
vesicles
(OMVs),
bacterial
ghosts
(BGs),
spores
(BSPs)─can
be
loaded
a
variety
antitumor
agents,
enabling
precise
targeting
sustained
release
within
microenvironment
(TME).
These
possess
intrinsic
properties
that
stimulate
immune
system,
enhancing
both
innate
adaptive
responses
to
further
amplify
therapeutic
effects.
The
ability
naturally
accumulate
hypoxic
regions
versatility
genetic
modifications
allow
tailored
strategies
synergistically
enhance
effectiveness
chemotherapy,
immunotherapy,
targeted
therapies.
This
review
comprehensively
examines
fundamental
principles
therapy,
focusing
on
employed
engineering,
loading,
use
therapy.
It
also
discusses
challenges
faced
optimizing
systems,
such
safety
concerns,
unintended
responses,
scalability
clinical
applications.
By
exploring
these
aspects,
this
provides
theoretical
framework
improving
bacterial-based
contributing
more
effective
personalized
treatments.
The
terrible
morbidity
and
mortality
of
malignant
tumors
urgently
require
innovative
therapeutics,
especially
for
apoptosis-resistant
tumors.
Pyroptosis,
a
pro-inflammatory
form
programmed
cell
death
(PCD),
is
featured
with
pore
formation
in
plasma
membrane,
swelling
giant
bubbles,
leakage
cytoplasmic
cytokines,
which
can
remodel
the
tumor
immune
microenvironment
by
stimulating
"cold"
to
be
an
immunogenic
"hot"
microenvironment,
consequently
augment
therapeutic
efficiency
Benefiting
from
current
advances
nanotechnology,
nanomedicine
extensively
applied
potentiate,
enable,
pyroptosis
enhancing
cancer-therapeutic
efficacy
specificity.
This
review
provides
concentrated
summary
discussion
most
recent
progress
achieved
this
emerging
field,
highlighting
nanomedicine-enabled/augmented
specific
strategy
favoring
construction
next-generation
nanomedicines
efficiently
induce
PCD.
It
highly
expected
that
further
clinical
translation
accelerated
inducing
pyroptotic
based
on
bioactive
nanomedicines.
Theranostics,
Год журнала:
2023,
Номер
13(5), С. 1571 - 1583
Опубликована: Янв. 1, 2023
Rationale:
Spatiotemporal
control
of
pyroptosis
has
a
profound
impact
on
cancer
immunotherapy.Owing
to
the
precise
spatiotemporal
and
reduction
in
side
effects
ultrasound
(US),
sonodynamic
therapy
(SDT)
is
expected
be
promising
mean
activate
pyroptosis.Furthermore,
pyroptosis-initiated
immune
response
can
amplified
by
enhanced
lymphocyte
infiltration
occurring
due
extracellular
matrix
(ECM)
depletion.Therefore,
it
highly
desirable
develop
sonodynamic-immunomodulatory
strategy
amplify
pyroptosis-mediated
tumor
immunotherapy
remodeling
microenvironment,
thereby
enhancing
immunotherapy.Methods:
We
reported
potent
based
sonosensitizer,
which
composed
LY364947-loaded
porous
coordination
network
(PCN-224)
camouflaged
with
red
blood
cell
(RBC)
membrane
evaluated
activation,
collagen
depletion,
immunocyte
infiltration,
adaptive
during
vitro
vivo.Results:
The
sonosensitizer
generated
reactive
oxygen
species
(ROS)
under
US
irradiation
initiated
caspase-3
apoptotic
signaling
pathway,
regarded
as
key
upstream
activator
gasdermin
E
(GSDME)-mediated
pyroptosis.During
subsequent
anti-tumor
mediated
pyroptosis,
LY364947
loosened
ECM
structure
via
resulting
T-lymphocyte
nearly
complete
eradication
tumors
mouse
model
formation
immunological
memory.
Conclusion:Our
findings
indicate
that
pyroptotic
exhibits
robust
efficacy
well
provides
novel
insights
into
role
immunology.
Abstract
Targeted
therapy
and
immunotherapy
have
brought
hopes
for
precision
cancer
treatment.
However,
complex
physiological
barriers
tumor
immunosuppression
result
in
poor
efficacy,
side
effects,
resistance
to
antitumor
therapies.
Bacteria‐mediated
provides
new
options
address
these
challenges.
Thanks
their
special
characteristics,
bacteria
excellent
ability
destroy
cells
from
the
inside
induce
innate
adaptive
immune
responses.
Furthermore,
bacterial
components,
including
vesicles,
spores,
toxins,
metabolites,
other
active
substances,
similarly
inherit
unique
targeting
properties
capabilities.
Bacteria
accessory
products
can
even
be
reprogrammed
produce
deliver
agents
according
clinical
needs.
This
review
first
discusses
role
of
different
development
tumorigenesis
latest
advances
bacteria‐based
delivery
platforms
existing
obstacles
application.
Moreover,
prospect
challenges
transformation
engineered
are
also
summarized.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 3, 2023
Immunotherapy
has
been
emerging
as
a
powerful
strategy
for
cancer
management.
Recently,
accumulating
evidence
demonstrated
that
bacteria-based
immunotherapy
including
naive
bacteria,
bacterial
components,
and
derivatives,
can
modulate
immune
response
via
various
cellular
molecular
pathways.
The
key
mechanisms
of
antitumor
immunity
include
inducing
cells
to
kill
tumor
directly
or
reverse
the
immunosuppressive
microenvironment.
Currently,
antigens
synthesized
vaccine
candidates
by
bioengineering
technology
are
novel
immunotherapy.
Especially
combination
therapy
with
conventional
therapies
may
further
achieve
enhanced
therapeutic
benefits
against
cancers.
However,
clinical
translation
is
limited
biosafety
concerns
non-uniform
production
standards.
In
this
review,
we
aim
summarize
strategies
based
on
advanced
therapeutics
discuss
their
potential
management,
will
also
propose
approaches
optimizing
facilitating
translation.
ACS Nano,
Год журнала:
2023,
Номер
17(2), С. 843 - 884
Опубликована: Янв. 4, 2023
Immunotherapy
continues
to
be
in
the
spotlight
of
oncology
therapy
research
past
few
years
and
has
been
proven
a
promising
option
modulate
one's
innate
adaptive
immune
systems
for
cancer
treatment.
However,
poor
delivery
efficiency
agents,
potential
off-target
toxicity,
nonimmunogenic
tumors
significantly
limit
its
effectiveness
extensive
application.
Recently,
emerging
biomaterial-based
drug
carriers,
including
but
not
limited
cells
bacteria,
are
expected
candidates
break
dilemma
immunotherapy,
with
their
excellent
natures
intrinsic
tumor
tropism
immunomodulatory
activity.
More
than
that,
tiny
vesicles
physiological
components
derived
from
them
have
similar
functions
source
due
inheritance
various
surface
signal
molecules
proteins.
Herein,
we
presented
representative
examples
about
latest
advances
employed
cells,
derivatives.
Simultaneously,
opportunities
challenges
bacteria-based
carriers
discussed
provide
reference
future
application
immunotherapy.