Journal of the American Chemical Society,
Год журнала:
2025,
Номер
147(9), С. 7360 - 7376
Опубликована: Фев. 15, 2025
Hypoxia,
a
hallmark
of
many
solid
tumors,
is
linked
to
increased
cancer
aggressiveness,
metastasis,
and
resistance
conventional
therapies,
leading
poor
patient
outcomes.
This
challenges
the
efficiency
photodynamic
therapy
(PDT),
which
relies
on
generation
cytotoxic
reactive
oxygen
species
(ROS)
through
irradiation
photosensitizer
(PS),
process
partially
dependent
levels.
In
this
work,
we
introduce
novel
family
potent
PSs
based
ruthenium(II)
polypyridyl
complexes
with
2,2′-bipyridyl
ligands
derived
from
COUPY
coumarins,
termed
COUBPYs.
Ru-COUBPY
exhibit
outstanding
in
vitro
cytotoxicity
against
CT-26
cells
when
irradiated
light
within
phototherapeutic
window,
achieving
nanomolar
potency
both
normoxic
hypoxic
conditions
while
remaining
nontoxic
dark,
impressive
phototoxic
indices
(>30,000).
Their
ability
generate
Type
I
II
ROS
underpins
their
exceptional
PDT
efficiency.
The
lead
compound
study,
SCV49,
shows
favorable
vivo
pharmacokinetic
profile,
excellent
toxicological
tolerability,
tumor
growth
inhibition
mice
bearing
subcutaneous
tumors
at
doses
as
low
3
mg/kg
upon
deep-red
(660
nm).
These
results
allow
us
propose
SCV49
strong
candidate
for
further
preclinical
development,
particularly
treating
large
tumors.
Abstract
Despite
the
advent
of
various
medical
interventions
for
cancer
treatment,
disease
continues
to
pose
a
formidable
global
health
challenge,
necessitating
development
new
therapeutic
approaches
more
effective
treatment
outcomes.
Photodynamic
therapy
(PDT),
which
utilizes
light
activate
photosensitizer
produce
cytotoxic
reactive
oxygen
species
(ROS)
eradicating
cells,
has
emerged
as
promising
approach
due
its
high
spatiotemporal
precision
and
minimal
invasiveness.
However,
widespread
clinical
use
PDT
faces
several
challenges,
including
inefficient
production
ROS
in
hypoxic
tumor
microenvironment,
limited
penetration
depth
biological
tissues,
inadequate
accumulation
photosensitizers
at
site.
Over
past
decade,
there
been
increasing
interest
utilization
photofunctional
transition
metal
complexes
applications
their
intriguing
photophysical
photochemical
properties.
This
review
provides
an
overview
current
design
strategies
used
innovative
phototherapeutics,
aiming
address
limitations
associated
with
achieve
The
challenges
future
perspectives
on
translation
are
also
discussed.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
It
is
highly
desired
to
achieve
Type-I
photosensitizer
(PS)
overcome
the
hypoxic
limitation
found
in
most
clinically
used
PSs.
Herein,
a
new
heavy-atom-free
PS
T-BNCy5
presented
by
incorporating
biotin-modified
naphthalimide
(NI)
unit
into
meso-position
of
N-benzyl-functionalized,
strongly
photon-capturing
pentamethine
cyanine
(Cy5)
dye.
Such
molecular
engineering
induces
rigid
orthogonal
geometry
between
NI
and
Cy5
units
introducing
an
intramolecular
sandwich-like
π-π
stacking
assembly,
which
effectively
promotes
intersystem
crossing
(ISC)
greatly
extends
triplet-state
lifetime
(τ
=
389
µs),
thereby
markedly
improving
superoxide
(O2
•-)-generating
ability.
In
vitro
assays
reveal
that
specifically
accumulates
mitochondria,
where
it
not
only
generates
O2
•-
under
photoirradiation
but
also
burst
cytotoxic
hydroxy
radical
(HO•)
cascade
biochemical
reactions,
ultimately
triggering
cell
ferroptosis
with
IC50
value
up
≈0.45
µm
whether
normoxia
or
hypoxia.
vivo
manifest
that,
benefiting
from
its
biotin
unit,
displays
strong
tumor-targeting
ability,
after
single
PDT
treatment,
can
ablate
tumor
almost
completely
be
cleared
body
through
biosafe
urinary
excretion,
indicating
potential
for
future
clinical
translation.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 15, 2025
Cancer
stem
cells
(CSCs)
are
key
contributors
to
tumor
resistance,
recurrence,
and
metastasis.
Conventional
chemotherapy
often
fails
target
eradicate
CSCs,
significantly
impairing
their
therapeutic
efficacy.
Herein,
we
design
synthesize
a
photoactivated
ferrocene-iridium(III)
complex
(Ir-3)
achieve
immunotherapy
against
melanoma
(including
cells).
In
short,
Ir-3
effectively
targets
mitochondria
dissociates
under
light
irradiation
produce
cytotoxic
Ir(III)
photosensitizer
Fe2+
ions.
They
can
generate
reactive
oxygen
species
by
the
Fenton
reaction,
robustly
induce
ferroptosis
autophagy,
eventually
trigger
immunogenic
cell
death
in
Furthermore,
exposure,
inhibits
cell-related
properties
promotes
macrophage-mediated
phagocytosis
of
cells.
For
vivo
studies,
is
encapsulated
DSPE-PEG
2000
form
tumor-targeting
Ir-3@PEG
nanoparticles.
After
photoactivation,
inhibit
primary
distant
tumors,
stemness
cells,
innate
adaptive
immune
responses.
