Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(15), С. 13383 - 13391
Опубликована: Июль 26, 2024
Photodynamic
therapy
(PDT)
is
a
promising
anticancer
method
due
to
its
noninvasive
features,
high
efficiency,
and
superior
accuracy.
The
activated
near-infrared
upconversion
photosensitizer
has
tissue
penetration
depth
could
be
explicitly
released
with
minimal
side
effects.
Therefore,
we
designed
synthesized
series
of
Br-substituted
compounds
(NFh-Br)
based
on
the
hemicyanine
dye.
heavy
atomic
effect
improves
generation
1O2
luminous
efficiency.
Especially,
NFh-Br11
exhibited
an
excellent
rate
under
808
nm
excitation
effectively
killed
tumor
cells
in
vitro,
alkaline
phosphatase
(ALP)-activatable
(NFh-ALP)
was
obtained
by
modifying
NFh-Br11.
NFh-ALP
ALP
release
NFh-Br11,
which
induces
apoptosis
outstanding
effects
vitro
vivo.
This
work
provide
strategy
for
designing
activatable
photosensitizers.
ACS Materials Letters,
Год журнала:
2024,
Номер
6(3), С. 969 - 975
Опубликована: Фев. 15, 2024
The
design
of
a
biologically
active
photosensitizer
that
effectively
combines
chemotherapy
and
photodynamic
therapy
remains
significant
challenge.
This
article
introduces
DNA
targeted
photosensitizer,
CQA,
which
integrates
the
alkylating
moiety
chlormethine
with
photosensitizing
moiety.
Through
damage
experiments
molecular
docking,
CQA
has
been
demonstrated
to
act
as
an
effective
targeting
damaging
chemotherapeutic
agent
via
chlormethine.
Meanwhile,
can
substantially
amplify
under
light
irradiation.
Such
enhancement
is
attributed
introduction
anthraquinone
group,
possesses
good
redox
properties
acts
electron
acceptor
promote
transfer.
Consequently,
efficiently
generates
both
type-I
type-II
reactive
oxygen
species
(ROS),
exerting
excellent
(PDT)
effect.
antitumor
efficacy
validated
results
from
in
vivo
tumor
growth
experiments,
H&E
staining,
IHC
analyses.
this
study
emphasizes
enhanced
ROS
generation,
underscoring
crucial
role
efficient
synergistic
chemo-
advancing
cancer
treatment
strategies.
Pharmaceutics,
Год журнала:
2023,
Номер
15(11), С. 2617 - 2617
Опубликована: Ноя. 11, 2023
Photodynamic
therapy
(PDT)
is
an
approved
therapeutic
procedure
that
exerts
cytotoxic
activity
towards
tumor
cells
by
activating
photosensitizers
(PSs)
with
light
exposure
to
produce
reactive
oxygen
species
(ROS).
Compared
traditional
treatment
strategies
such
as
surgery,
chemotherapy,
and
radiation
therapy,
PDT
not
only
kills
the
primary
tumors,
but
also
effectively
suppresses
metastatic
tumors
immune
response.
However,
anti-tumor
effects
induced
are
influenced
several
factors,
including
localization
of
PSs
in
cells,
concentration,
fluence
rate
light,
integrity
function.
In
this
review,
we
systematically
summarize
influence
factors
mediated
PDT.
Furthermore,
update
on
combination
other
immunotherapy
provided.
Finally,
future
directions
challenges
immunity
discussed.
Advanced Functional Materials,
Год журнала:
2023,
Номер
34(12)
Опубликована: Дек. 15, 2023
Abstract
Photosensitizers
(PSs)
with
effective
reactive
oxygen
species
generation
ability
against
hypoxia
are
of
great
potential
for
clinical
treatment
malignant
tumors.
However,
complex
tumor
microenvironment,
such
as
antioxidative
responses
and
immunosuppression,
would
ineluctably
limit
the
efficiency
photodynamic
therapy
(PDT).
Herein,
a
molecular‐targeting
photosensitizer
QTANHOH
is
rationally
designed
histone
deacetylases
(HDACs‐targeting
photo‐immunotherapy
application.
The
PS
displays
excellent
type‐I/II
PDT
performance,
exhibiting
significant
phototoxicity
toward
cancer
cells
half
maximal
inhibitory
concentration
(IC
50
)
less
than
10
n
m
in
both
normoxia
conditions
under
blue
laser
irradiation.
Moreover,
bioactive
compound
could
inhibit
HDACs
activate
immune
microenvironment
to
boost
efficacy
on
immunocompetent
BALB/c
mice
breast
cancer,
leading
eradication
solid
inhibition
metastasis.
Notably,
introduces
an
alternative
strategy
achieve
superior
phototherapy
therapy.
Nanoscale Horizons,
Год журнала:
2024,
Номер
9(9), С. 1390 - 1416
Опубликована: Янв. 1, 2024
Molecular
disassembly
is
pioneering
a
new
route
to
refined
diagnostic
and
therapeutic
solutions.
This
approach
breaks
down
self-assembled
molecules,
offering
enhanced
precision
efficiency
in
various
bio-oriented
applications.
Chemical Science,
Год журнала:
2024,
Номер
15(12), С. 4519 - 4528
Опубликована: Янв. 1, 2024
In
this
work,
the
topological
effect
on
binding
interaction
between
a
G-quadruplex
and
thioflavin
T
(ThT)
ligand
was
systematically
investigated
platform
of
an
intramolecular
split
(Intra-SG).
Distinct
fluorescence
changes
from
ThT
were
presented
in
presence
distinct
modes
Intra-SG
structures
intriguing
phenomenon
target-induced
light-up
occurred
for
2
:
10,
5
7
8
4.
It
validated
that
hybridization
spacer
target
did
not
unfold
G-quadruplex,
but
facilitated
binding.
Moreover,
3'
guanine-rich
fragment
very
susceptible
to
topology
variation
produced
by
bound
strand.
Additionally,
bioanalytical
method
developed
ultrasensitive
gene
detection,
confirming
utility
ThT/Intra-SG
complex
as
universal
signal
transducer.
is
believed
results
disclosed
rules
will
inspire
researchers
develop
many
new
DNA-based
transducers
future.
Dalton Transactions,
Год журнала:
2024,
Номер
53(17), С. 7282 - 7291
Опубликована: Янв. 1, 2024
Transition
metal
complexes
containing
the
qtpy
ligand
with
high-energy
excited
states
are
reported.
Binding
studies
duplex
and
quadruplex
DNA
showed
a
preference
for
Ir(
iii
)
as
groove
binders
to
structures.
ACS Pharmacology & Translational Science,
Год журнала:
2024,
Номер
7(7), С. 2174 - 2184
Опубликована: Июнь 20, 2024
G-quadruplexes
(G4s)
are
potential
drug
targets
in
cancer
treatment.
However,
the
G4-targeted
ligands
seem
to
lack
sufficient
selectivity
between
tumors
and
normal
tissues,
appealing
for
a
new
modified
anticancer
strategy
on
basis
of
them.
Type-1
photodynamic
therapy
(PDT)
is
promising
possessing
excellent
spatiotemporal
precision
solid
with
hypoxic
microenvironment.
type-1
photosensitizers
that
target
G4s
induce
situ
photodamage
have
never
been
previously
reported.
In
this
study,
we
reported
photosensitizer
based
G4-targeted,
high-contrast
fluorescent
ligand
(TR2).
The
subsequent
studies
demonstrated
TR2
could
transfer
from
lysosomes
nuclei
elevated
G4
formation
as
well
DNA
damage
upon
irradiation.
Notably,
it
was
observed
may
not
activate
repair
machinery
irradiation,
suggesting
durable,
strong
effect
inducing
damage.
Consequently,
light-irradiated
exhibited
photocytotoxicity
triple-negative
breast
cell
proliferation
(at
nanomolar
concentration)
showed
obvious
inhibition
growth
three-dimensional
(3D)
tumor
spheroids.
Finally,
RNA-seq
analysis
TR2-mediated
PDT
negative
impact
enhancing
antitumor
immunity
pathways.
Overall,
study
provided
chemical
tool
image-guided
PDT.
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.
