Subcellular visualization: Organelle-specific targeted drug delivery and discovery
Advanced Drug Delivery Reviews,
Год журнала:
2023,
Номер
199, С. 114977 - 114977
Опубликована: Июнь 28, 2023
Язык: Английский
Transforming Toxicity Assessment through Microphysiology, Bioprinting, and Computational Modeling
Advances in Clinical Toxicology,
Год журнала:
2024,
Номер
9(1), С. 1 - 14
Опубликована: Янв. 1, 2024
Background:
Traditional
toxicity
testing
emphasizes
animal
models
with
growing
concerns
regarding
predictive
capacity,
throughput
and
ethics.
Rapid
innovation
surrounding
human
cell
platforms,
bioengineered
tissues,
omics
techniques
computational
tools
offers
more
modern
alternatives
aligned
expanding
knowledge
of
chemical
biological
pathways.
These
disruptive
approaches
promise
immense
potential
to
transform
next-generation
safety
assessment
drug
development
pipelines.
Purpose:
This
review
provides
clinical
researchers
an
updated,
comprehensive
perspective
across
evolving
areas
focus
in
new
methods
analysis
latest
advances
translational
context.
Main
Body:
We
survey
progress
two-
three-dimensional
cultures
recapitulating
tissue/organ
complexity
impossible
conventional
assays.
Complementing
this,
modeling
integrates
structure-activity
relationships,
physicochemical
properties
physiological
interactions
predict
pharmacokinetics
silico.
Expanding
model
organisms
add
further
dimensionality
demographic
relevance.
High-throughput
imaging
technologies
unravel
mechanisms
illuminate
biomarkers
undetectable
by
standard
measures.
Specialized
show
high
addressing
toxicodynamic
intricacies
within
disease
contexts
like
diabetes
NAFLD.
Evaluating
traditional
medicines
phytochemicals
likewise
represents
area
growth
well-suited
for
contemporary
platforms.
Future
outlook
weighs
remarkable
advantages
reducing
demands,
enabling
precision
toxicology
links
medicine
overhauling
core
risk
frameworks.
Conclusion:
intends
catalyze
discourse
on
strategic
optimization
priorities
roadmaps
towards
fully
unlocking
the
yet
still
emerging
public
health
these
poising
transformation
sciences
centered
human-focused
models.
Язык: Английский
Recapitulating the Drifting and Fusion of Two-Generation Spheroids on Concave Agarose Microwells
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(15), С. 11967 - 11967
Опубликована: Июль 26, 2023
Cells
with
various
structures
and
proteins
naturally
come
together
to
cooperate
in
vivo.
This
study
used
cell
spheroids
cultured
agarose
micro-wells
as
a
3D
model
the
movement
of
cells
or
toward
other
spheroids.
The
formation
dynamics
tumor
interactions
two
batches
were
studied.
results
showed
that
concave
bottom
micro-well
(diameter:
2
mm,
depth:
mm)
prepared
from
3%
could
be
interaction
cells.
initial
numbers
5
×
103
cells/well
6
104
all
form
after
3
days
incubation.
Adding
second
batch
DU
145
existing
spheroid
resulted
satellite
around
parental
spheroid.
Complete
fusion
generation
was
observed
when
formed
1
cells,
per
well.
A
higher
amount
(1
cell/well)
led
independent
48
h
co-culture,
suggesting
behavior
towards
depended
on
factors,
such
volume
number
between
Human
Umbilical
Vein
Endothelial
(HUVECs)
modeled
micro-wells.
HUVECs
(3
gather
104,
well
rather
than
aggregate
their
own
HUVEC
highlights
importance
analyzing
biological
properties
before
designing
experimental
procedures
for
sequential
further
emphasizes
significant
roles
density
play
determining
location
Язык: Английский
Doxorubicin-sensitive and -resistant colorectal cancer spheroid models: assessing tumor microenvironment features for therapeutic modulation
Frontiers in Cell and Developmental Biology,
Год журнала:
2023,
Номер
11
Опубликована: Дек. 22, 2023
Introduction:
The
research
on
tumor
microenvironment
(TME)
has
recently
been
gaining
attention
due
to
its
important
role
in
growth,
progression,
and
response
therapy.
Because
of
this,
the
development
three-dimensional
cancer
models
that
mimic
interactions
TME
structure
complexity
is
great
relevance
drug
development.
Methods:
This
study
aimed
characterize
colorectal
spheroids
overtime
assess
how
susceptibility
or
resistance
doxorubicin
(Dox)
inclusion
fibroblasts
heterotypic
influence
modulate
their
secretory
activity,
namely
release
extracellular
vesicles
(EVs),
Dox-mediated
chemotherapy.
Different
characteristics
were
assessed
over
time,
spheroid
viability,
presence
hypoxia,
expression
hypoxia
inflammation-associated
genes
proteins.
Due
importance
EVs
biomarker
discovery
with
impact
early
diagnostics,
prognostics
treatment,
proteomic
profiling
released
by
different
3D
was
also
assessed.
Response
treatment
monitored
assessing
Dox
internalization
effects
structures
cell
viability.
Results
Discussion:
results
show
distinct
features
are
affected
both
fibroblasts.
Fibroblasts
can
stabilize
models,
through
modulation
inflammation
levels,
as
well
expressions
associated
transcripts/proteins,
promotes
alterations
protein
profile
exhibit
EVs.
Summarily,
increase
cell-cell
cell-extracellular
matrix
interactions,
making
a
model
understand
chemotherapies
resistance.
induction
shown
Dox,
especially
homotypic
spheroids,
it
viability
consequently
chemoresistance
those
when
exposed
Dox.
Taken
together
these
highlight
finding
characterizing
resembling
more
closely
vivo
tumors
modulating
Язык: Английский
Method for Culturing and Imaging Homogeneous 3D Cancer Spheroids as a Model for the Uptake of DNA Nanostructures
Methods in molecular biology,
Год журнала:
2025,
Номер
unknown, С. 167 - 178
Опубликована: Янв. 1, 2025
Язык: Английский
Organoid in Droplet: Production of Uniform Pancreatic Cancer Organoids from Single Cells
Materials Today Bio,
Год журнала:
2025,
Номер
32, С. 101765 - 101765
Опубликована: Апрель 12, 2025
Язык: Английский
Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds
Claire Blanchard,
Alison T. Gomeiz,
Kyle Avery
и другие.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Июль 26, 2024
Abstract
Background
Tumor
heterogeneity
is
a
main
contributor
of
resistance
to
anti-cancer
targeted
agents
though
it
has
proven
difficult
study.
Unfortunately,
model
systems
functionally
characterize
and
mechanistically
study
dynamic
responses
treatment
across
coexisting
subpopulations
cancer
cells
remain
missing
need
in
oncology.
Methods
Using
single
cell
cloning
expansion
techniques,
we
established
monoclonal
(MCPs)
from
commercially
available
epidermal
growth
factor
receptor
(EGFR)-mutant
non-small
lung
line.
We
then
used
this
sensitivity
the
EGFR
inhibitor
osimertinib
populations
within
same
tumor.
Pathway-centered
signaling
dynamics
associated
with
response
morphological
characteristics
MCPs
were
assessed
using
Reverse
Phase
Protein
Microarray.
Signaling
nodes
differentially
activated
less
sensitive
pharmacologically
inhibited
identify
target
proteins
putatively
implicated
promoting
drug
resistance.
Results
demonstrated
highly
heterogeneous
sensitivities
osimertinib.
Cell
viability
after
increased
>
20%
compared
parental
line
selected
MCPs,
whereas
decreased
by
75%
other
MCPs.
Reduced
was
detected
higher
proliferation
rates,
L858R
expression,
activation
binding
partners
downstream
molecules,
expression
epithelial-to-mesenchymal
transition
markers.
Levels
MCPs’
rates
also
c-MET
IGFR
inhibitors.
Conclusions
represent
suitable
system
biomolecular
behaviors
preclinical
studies
test
biological
mechanisms
therapeutics.
Язык: Английский
Mitochondria Localized Anticancer Iridium(III) Prodrugs for Targeted Delivery of Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors and Cytotoxic Iridium(III) Complex
Inorganic Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 12, 2024
Myeloid
cell
leukemia-1
(Mcl-1)
is
an
antiapoptotic
oncoprotein
overexpressed
in
several
malignancies
and
acts
as
one
of
the
promising
therapeutic
targets
for
cancer.
Even
though
there
are
small
molecule
based
Mcl-1
inhibitors
reported,
delivery
inhibitor
at
target
site
quite
challenging.
In
this
regard,
we
developed
a
series
mitochondria
targeting
luminescent
cyclometalated
iridium(III)
prodrugs
bearing
via
ester
linkage
due
to
presence
protein
outer
mitochondrial
membrane.
Among
synthesized
prodrugs,
IrThpy@L2
was
found
exhibit
potent
cytotoxicity
(IC
Язык: Английский