Drug Delivery System Targeting Cancer-Associated Fibroblast for Improving Immunotherapy
International Journal of Nanomedicine,
Год журнала:
2025,
Номер
Volume 20, С. 483 - 503
Опубликована: Янв. 1, 2025
Abstract:
Cancer-associated
fibroblasts
(CAFs)
are
a
heterogeneous
population
of
non-malignant
cells
that
play
crucial
role
in
the
tumor
microenvironment,
increasingly
recognized
as
key
contributors
to
cancer
progression,
metastasis,
and
treatment
resistance.
So,
targeting
CAFs
has
always
been
considered
an
important
part
immunotherapy.
However,
improve
efficacy
therapy
is
currently
major
challenge.
Nanomaterials
show
their
unique
advantages
whole
process.
At
present,
nanomaterials
have
achieved
significant
accomplishments
medical
applications,
particularly
field
cancer-targeted
therapy,
showing
enormous
potential.
It
confirmed
can
not
only
directly
target
CAFs,
but
also
interact
with
microenvironment
(TME)
immune
affect
tumorigenesis.
As
for
treatment,
could
enhance
therapeutic
effect
many
ways.
Therefore,
this
review,
we
first
summarized
current
understanding
complex
interactions
between
TME,
cells,
cells.
Next,
discussed
common
modern
medicine
respective
impacts
on
tumors.
Finally,
focus
application
nano
drug
delivery
system
therapy.
Keywords:
cancer-associated
fibroblasts,
delivery,
nanomedicine,
immunotherapy
Язык: Английский
Nanomaterials in cancer immunotherapy: targeting cancer-associated fibroblasts
Cancer Nanotechnology,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 17, 2025
Emphasizing
the
significance
of
cancer-associated
fibroblasts
(CAFs),
non-malignant
yet
pivotal
players
within
tumor
microenvironment
(TME),
this
review
illuminates
role
inflammatory
subtype
(iCAF)
as
catalysts
in
cancer
proliferation,
metastasis,
and
therapeutic
resistance.
Given
their
paramount
importance,
targeting
CAFs
emerges
a
robust
strategy
evolving
landscape
immunotherapy.
Nanomaterials,
distinguished
by
unique
features
malleability,
hold
considerable
promise
biomedicine,
especially
precision-oriented
domain
therapy.
Their
aptitude
for
modulating
immune
responses,
amplifying
drug
efficacy
through
precise
delivery,
discerningly
focusing
on
cells
TME
situates
nanomaterials
formidable
tools
to
transcend
boundaries
set
conventional
treatments.
This
scrutinizes
convoluted
interplay
among
CAFs,
cells,
TME.
It
further
showcases
widely
utilized
management.
We
underscore
potential
nanoscale
delivery
systems
directed
at
underscoring
transformative
power
revolutionizing
therapies,
enhancing
precision,
culminating
improved
patient
outcomes.
Язык: Английский
Innovative Strategies to Combat 5-Fluorouracil Resistance in Colorectal Cancer: The Role of Phytochemicals and Extracellular Vesicles
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 7470 - 7470
Опубликована: Июль 8, 2024
Colorectal
cancer
(CRC)
is
a
significant
public
health
challenge,
with
5-fluorouracil
(5-FU)
resistance
being
major
obstacle
to
effective
treatment.
Despite
advancements,
5-FU
remains
formidable
due
complex
mechanisms
such
as
alterations
in
drug
transport,
evasion
of
apoptosis,
dysregulation
cell
cycle
dynamics,
tumor
microenvironment
(TME)
interactions,
and
extracellular
vesicle
(EV)-mediated
pathways.
Traditional
chemotherapy
often
results
high
toxicity,
highlighting
the
need
for
alternative
approaches
better
efficacy
safety.
Phytochemicals
(PCs)
EVs
offer
promising
CRC
therapeutic
strategies.
PCs,
derived
from
natural
sources,
exhibit
lower
toxicity
can
target
multiple
pathways
involved
progression
resistance.
facilitate
targeted
delivery,
modulate
immune
response,
interact
TME
sensitize
cells
However,
potential
PCs
engineered
overcoming
reshaping
immunosuppressive
underexplored.
Addressing
this
gap
crucial
identifying
innovative
therapies
enhanced
reduced
toxicities.
This
review
explores
multifaceted
evaluates
synergistic
effects
combining
improve
treatment
while
minimizing
adverse
effects.
Additionally,
it
investigates
by
serving
delivery
vehicles
modulating
TME.
By
synthesizing
current
knowledge
addressing
research
gaps,
enhances
academic
understanding
CRC,
interdisciplinary
involving
revolutionizing
therapy.
Further
clinical
validation
are
essential
translating
these
findings
into
improved
patient
outcomes.
Язык: Английский
Cancer-Associated-Fibroblast-Mediated Paracrine and Autocrine SDF-1/CXCR4 Signaling Promotes Stemness and Aggressiveness of Colorectal Cancers
Cells,
Год журнала:
2024,
Номер
13(16), С. 1334 - 1334
Опубликована: Авг. 12, 2024
Colorectal
cancer
(CRC)
is
a
leading
cause
of
mortality
worldwide,
and
cancer-associated
fibroblasts
(CAFs)
play
major
role
in
the
tumor
microenvironment
(TME),
which
facilitates
progression
CRC.
It
critical
to
understand
how
CAFs
promote
CRC
for
development
novel
therapeutic
approaches.
The
purpose
this
study
was
CAF-derived
stromal-derived
factor-1
(SDF-1)
its
interactions
with
corresponding
C-X-C
motif
chemokine
receptor
4
(CXCR4)
progression.
Our
focused
on
their
roles
promoting
cell
migration
invasion
effects
characteristics
stem
cells
(CSCs),
ultimately
impact
patient
outcomes.
Here,
using
vivo
approaches
clinical
histological
samples,
we
analyzed
influence
secreted
SDF-1
progression,
especially
terms
behavior
stemness.
We
demonstrated
that
CAF-secreted
significantly
enhanced
through
paracrine
signaling.
In
addition,
overexpression
lines
HT29
HCT-116
triggered
these
generate
autocrine
signaling,
further
CSC
characteristics,
including
those
migration,
invasion,
spheroid
formation.
An
immunohistochemical
showed
close
relationship
between
CXCR4
expression
tissue,
affected
administration
AMD3100,
an
inhibitor
CXCR4,
reversed
entire
phenomenon.
results
strongly
suggest
targeting
signaling
axis
feasible
approach
attenuating
it
may,
therefore,
serve
as
alternative
treatment
method
improve
prognosis
patients
CRC,
advanced,
recurrent,
or
metastatic
following
standard
therapy.
Язык: Английский
Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets
Non-coding RNA Research,
Год журнала:
2023,
Номер
8(4), С. 615 - 632
Опубликована: Сен. 11, 2023
Colorectal
cancer
(CRC)
is
ranked
as
the
world's
third-most
prevalent
cancer,
and
metastatic
CRC
considerably
increases
cancer-related
fatalities
globally.
A
number
of
complex
mechanisms
that
are
strictly
controlled
at
molecular
level
involved
in
metastasis,
which
primary
reason
for
death
people
with
CRC.
Recently,
it
has
become
clear
exosomes,
small
extracellular
vesicles
released
by
non-tumorous
tumorigenic
cells,
play
a
critical
role
communication
mediators
among
tumor
microenvironment
(TME).
To
facilitate
between
TME
non-coding
RNAs
(ncRNAs)
crucial
recognized
potent
regulators
gene
expression
cellular
processes,
such
metastasis
drug
resistance.
NcRNAs
now
many
hallmarks
including
metastasis.
Exosomal
ncRNAs,
like
miRNAs,
circRNAs,
lncRNAs,
have
been
demonstrated
to
influence
contribute
However,
link
exosomal
ncRNAs
not
well
understood.
This
review
highlights
essential
roles
progression
disease
explores
therapeutic
choices
open
patients
who
metastases.
ncRNA
treatment
strategy
development
still
its
early
phases;
consequently,
additional
investigation
required
improve
delivery
methods
find
novel
targets
confirm
effectiveness
safety
these
therapies
preclinical
clinical
contexts.
Язык: Английский
Exosomes derived from colorectal cancer cells take part in activation of stromal fibroblasts through regulating PHLPP isoforms.
PubMed,
Год журнала:
2024,
Номер
23, С. 634 - 654
Опубликована: Янв. 1, 2024
Given
that
tumor
cells
primarily
instigate
systemic
changes
through
exosome
secretion,
our
study
delved
into
the
role
of
colorectal
cancer
(CRC)-secreted
exosomal
miR-224
in
stromal
reprogramming
and
its
impact
on
endothelial
cell
angiogenesis.
Furthermore,
we
assessed
potential
clinical
significance
a
specific
signature
circulating
serum-derived
miRNAs,
serving
as
non-invasive
biomarker
for
CRC
diagnosis.
Circulating
miR-103a-3p,
miR-135b-5p,
miR-182-5p,
miR-224-5p
were
significantly
up-regulated,
while
miR-215-5p,
miR-455-5p
showed
significant
down-regulation
patients
than
healthy
individuals.
Our
findings
indicated
expressions
CAF-specific
markers
(α-SMA
FAP)
CAF-derived
cytokines
(IL-6,
SDF-1)
induced
fibroblasts
stimulated
with
SW480
exosomes,
partly
due
to
Akt
activation.
As
plausible
mechanism,
transfer
from
SW40
may
activate
fibroblasts,
which
turn,
promote
sprouting.
The
identified
PHLPP1
PHLPP2
direct
targets
demonstrated
CRC-secreted
activates
signaling
by
regulating
PHLPP1/2
activated
thereby
affecting
proliferation
migration.
This
established
panel
six-circulating
miRNAs
Also,
proposed
supporting
model
takes
part
CAFs
signaling.
affect
malignant
biological
behavior
elicit
vascular
response
within
microenvironment
cells.
See
also
graphical
abstract(Fig.
1).
Язык: Английский
Single-cell immune escape correlation analysis: unraveling the prognostic influence of intercellular communication in the tumor microenvironment of colorectal cancer
Qixin Gan,
Haifen Liu,
Fangting Tang
и другие.
Aging,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 29, 2024
Background:
The
role
of
immune
escape-related
genes
in
the
tumor
microenvironment
(TME)
CRC
remains
unclear
but
is
known
to
be
crucial
for
development.
Methods:
We
analyzed
single-cell
RNA-seq
data
from
13
samples,
comprising
66,050
cells,
using
NMF
identify
genes.
predicted
prognosis
and
response
novel
TME
cell
clusters
a
public
cohort
immunotherapy
cohort.
Results:
analysis
revealed
distinct
types,
including
plasma
epithelial
T
NK
goblet
intestinal
B
macrophages,
fibroblasts,
endothelial
mast
cells.
These
types
were
further
grouped
into
new
based
on
gene
annotations.
Immunohistochemistry
(IHC)
confirmed
high
expression
TGF-β+,
JAK1+,
Calretinin+
tissues,
validating
key
bioinformatics
findings
their
potential
relevance
pathology.
Pseudo-temporal
trajectory
showed
differentiation
different
subtype
clusters.
Cellular
communication
extensive
interactions
between
cells
metabolizing
cell-related
subtypes.
SCENIC
identified
transcription
factors
upstream
with
varying
responses.
Moreover,
associated
escape
processes
exhibited
enrichment
CAF
subtypes,
CD8-depleted,
M1,
M2
macrophages.
Bulk-seq
demonstrated
significant
prognostic
importance
CRC.
Remarkably,
response,
especially
patients
treated
ICB,
involving
CAFs,
Conclusion:
Our
study
first
reveal
mediating
intercellular
within
microenvironment,
elucidating
anti-tumor
mechanisms
responses
cluster
Язык: Английский