Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(44), С. 30033 - 30045
Опубликована: Окт. 28, 2024
Cuproptosis,
a
recently
identified
form
of
copper-dependent
cell
death,
shows
promising
tumor
suppressive
effects
with
minimal
drug
resistance.
However,
its
therapeutic
efficacy
is
hampered
by
dependence
on
copper
ions
and
the
glutathione
(GSH)-rich
microenvironment
in
tumors.
Here,
we
have
developed
polyvalent
aptamer
nanodrug
conjugates
(termed
CuPEs@PApt)
nucleosome-like
structure
to
improve
cuproptosis
therapy
exploiting
mitochondrial
overload
GSH
depletion.
Polyvalent
(PApt),
comprising
epithelial
adhesion
molecule
aptamers
for
targeting
repetitive
PolyT
sequences
chelation,
facilitates
efficient
loading
targeted
delivery
peroxide-Elesclomol
nanodots
(CuPEs).
Upon
internalization
cells,
Elesclomol
released
from
CuPEs@PApt
accumulates
mitochondria
initiate
cuproptosis,
while
lysosomal
degradation
CuP
generates
exogenous
Cu2+
H2O2,
triggering
Fenton-like
reaction
depletion
enhance
cuproptosis.
In
vitro
vivo
experiments
confirm
this
strategy
inducing
immunogenic
latter
contributing
activation
antitumor
immune
response
synergistic
growth
inhibition.
Chemical Society Reviews,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
This
review
provides
a
comprehensive
summary
of
the
dysregulation
redox
metabolism
in
cancer
cells
and
advantages
latest
advances
nanomaterial-assisted
metabolic
regulation
therapy.
Materials Horizons,
Год журнала:
2024,
Номер
11(18), С. 4275 - 4310
Опубликована: Янв. 1, 2024
This
comprehensive
review
systematically
summarizes
the
intrinsic
mechanism
of
different
metal
ion
(such
as
Fe
3+
/Fe
2+
,
Cu
/Cu
+
Ca
Zn
Mn
Na
/K
and
Mg
)-mediated
interference
therapies
their
research
progress
in
cancer
treatment.
Nano-Micro Letters,
Год журнала:
2024,
Номер
16(1)
Опубликована: Авг. 13, 2024
Abstract
The
eye,
a
complex
organ
isolated
from
the
systemic
circulation,
presents
significant
drug
delivery
challenges
owing
to
its
protective
mechanisms,
such
as
blood-retinal
barrier
and
corneal
impermeability.
Conventional
administration
methods
often
fail
sustain
therapeutic
levels
may
compromise
patient
safety
compliance.
Polysaccharide-based
microneedles
(PSMNs)
have
emerged
transformative
solution
for
ophthalmic
delivery.
However,
comprehensive
review
of
PSMNs
in
ophthalmology
has
not
been
published
date.
In
this
review,
we
critically
examine
synergy
between
polysaccharide
chemistry
microneedle
technology
enhancing
ocular
We
provide
thorough
analysis
PSMNs,
summarizing
design
principles,
fabrication
processes,
addressed
during
fabrication,
including
improving
comfort
also
describe
recent
advances
performance
various
both
research
clinical
scenarios.
Finally,
current
regulatory
frameworks
market
barriers
that
are
relevant
commercial
advancement
final
perspective
on
area.
Abstract
Immunotherapy
is
a
promising
new
approach
for
tumor
treatment.
However,
its
clinical
application
hindered
by
insufficient
immunogenicity,
hypoxia,
and
immunosuppressive
microenvironment
(TME).
Here,
oxygen
pump
microneedles
(OPMNs)
loaded
with
zinc‐doped
copper
sulfide
nanoflowers
(ZCS
NFs)
PD‐L1
small
interfering
RNA
(siPD‐L1)
(OPMNs‐ZCS@siPD‐L1)
are
developed
boosting
immunotherapy.
OPMN‐ZCS@siPD‐L1
enhances
immunogenicity
through
ZCS
NFs
inducing
cuproptosis,
reverses
TME
siPD‐L1,
promotes
drug
penetration,
ameliorates
hypoxia
bubbles.
More
importantly,
cuproptosis‐induced
mitochondrial
DNA
(mtDNA)
together
Zn
2+
co‐activate
the
STING
pathway,
triggering
robust
immune
response.
increases
sensitivity
to
cuproptosis
induces
immunogenic
cell
death
(ICD)
in
vivo
vitro,
which
significantly
inhibits
progression
metastasis.
The
novel
strategy
of
“increasing
throttle”
(cuproptopsis‐mediated
activation
&
ICD
effect)
combined
“releasing
brake”
(PD‐L1
inhibition
improvement)
provides
enhancing
percutaneous
Angewandte Chemie International Edition,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 9, 2025
Albumin-based
drug
delivery
system,
exemplified
by
FDA-approved
treatments
like
Abraxane,
have
demonstrated
significant
potential
in
cancer
therapy.
However,
albumin
carriers
still
suffer
from
poor
tumor-targeting
capability,
leading
to
low
efficacy
and
systemic
side
effects
on
healthy
cells
applications.
Here,
we
report
a
general
method
for
modification
of
drugs
aptamer
coating
shell
that
are
hydrophobically
inserted
into
the
surface,
constructing
drugs-cored
spherical
nucleic
acid
(adSNA).
This
adSNA
platform
allows
versatile
loading
various
therapeutic
agents,
including
chemotherapy
drugs,
polyphenols,
cuproptosis
inducers,
near-infrared
(NIR)
photosensitizers,
enabling
targeted
tumor
delivery.
Compared
with
covalent
method,
hydrophobic
insertion
has
been
proven
be
greater
simplicity,
higher
aptamer-grafting
efficiency,
superior
capabilities,
comparable
stability
under
physiological
conditions.
In
proof-of-concept
study,
delivered
NIR-II
photothermal
agents
heat
shock
protein
inhibitors
tumor-specific
mild
traditional
therapy
(PTT),
this
approach
utilizes
PTT
achieve
tissue
penetration
while
downregulating
proteins
cells,
resulting
precise
thermal
ablation
at
lower
temperatures.
addition,
adSNAs
straightforward
synthesize
scalable
large-scale
production,
offering
advance
development
clinical
drugs.
Cuproptosis,
a
distinct
cell
death
pathway,
has
been
integrated
into
nanomedicine
for
disease
theranostics.
However,
current
nanosystems
inducing
cuproptosis
rely
on
exogenous
toxic
copper
ions,
limiting
the
scope
of
biomaterials.
Developing
nanoplatforms
that
induce
without
holds
substantial
promise.
Here,
we
engineered
two-dimensional
iron
(Fe)
single-atom–doped
molybdenum
disulfide
(MoS
2
)
piezocatalyst
(Fe-MoS
tumor
therapy.
Incorporating
single
Fe
atoms
enhances
MoS
piezoelectric
polarization
via
charge
redistribution
and
modulates
Mo
oxidation
states,
enabling
multifaceted
enzymatic
activities,
including
peroxidase-,
glutathione
oxidase–,
oxidase-,
catalase-like
activities.
Upon
ultrasound
stimulation,
Fe-MoS
nanocatalyst
generates
reactive
oxygen
species
depletes
synergistic
piezocatalytic
enzyocatalytic
effects,
disrupting
ion
homeostasis
cuproptosis,
concurrently
triggering
ferroptosis
ferritinophagy,
which
collectively
suppression.
This
study
represents
first
paradigm
to
introduce
copper-free
initiating
substantially
advancing
applications
in
Platinum
(Pt)-based
chemotherapeutic
agents,
known
for
their
potent
cytotoxicity,
are
extensively
used
in
clinical
oncology.
However,
therapeutic
efficacy
is
severely
limited
by
a
variety
of
factors,
particularly
the
hypoxic
tumor
microenvironment
(TME),
which
not
only
impedes
effective
drug
delivery
but
also
triggers
immune
suppression,
further
diminishing
antitumor
effects
Pt
drugs.
In
response
to
these
challenges,
we
have
developed
biotin
receptor
(BR)-targeting
oxaliplatin
(OXA)-based
PtIV
prodrug,
named
Lipo-OPtIV-BT,
could
encapsulate
hemoglobin
(Hb)
as
an
oxygen
carrier,
forming
PtIV-loaded
lipid
nanoparticles
(Hb@BTOPtIV).
The
design
Hb@BTOPtIV
aims
address
dual
issues
poor
and
suppression
effectively
increasing
local
tension
TME.
Notably,
our
findings
demonstrate
that
cytotoxic
BR-targeting
prodrug
increased
levels
synergistically
reverse
microenvironment,
leading
improved
efficacy.
We
observed
significantly
biodistribution
drug,
enabling
it
preferentially
accumulate
regions.
Importantly,
enhanced
oxygenation
within
TME
plays
critical
role
reshaping
landscape
tumor,
promoting
more
favorable
environment
chemotherapy.
This
reversal
evidenced
infiltration
T
cells
reduced
regulatory
(Tregs)
tumor.
These
highlight
promising
potential
using
amphiphiles
improve
accumulation
at
sites
counteract
immunosuppression
induced
hypoxia.
