ACS Applied Materials & Interfaces,
Год журнала:
2022,
Номер
14(45), С. 51200 - 51211
Опубликована: Ноя. 3, 2022
Prodrug-based
self-assembled
nanoparticles
combined
with
the
merits
of
nanotechnology
and
prodrugs
strategies
have
gradually
become
a
research
trending
topic
in
field
drug
delivery.
These
usually
consist
parent
drugs,
connecting
bonds,
modifying
chains.
The
influences
bonds
chains
on
pharmaceutical
characteristics,
vivo
delivery
fate,
antitumor
activity
prodrug
nanoassemblies
remain
elusive.
Herein,
three
docetaxel
(DTX)
were
designed
using
sulfur
(thioether
bond
or
disulfide
bond)
as
fatty
alcohols
(straight
chain
branched
chain)
Interestingly,
difference
between
deeply
influenced
colloidal
stability,
redox
responsive
release,
cytotoxicity,
pharmacokinetic
properties,
tumor
accumulation,
effect
nanoassemblies.
DTX
conjugated
via
(HUA-SS-DTX)
significantly
improved
efficiency
reduced
systematic
toxicity.
Our
study
elaborates
vital
role
rational
design
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(3), С. 101432 - 101432
Опубликована: Фев. 21, 2024
Dimeric
prodrug
nanoassemblies
(DPNAs)
stand
out
as
promising
strategies
for
improving
the
efficiency
and
safety
of
chemotherapeutic
drugs.
The
success
trisulfide
bonds
(-SSS-)
in
DPNAs
makes
polysulfide
a
worthwhile
focus.
Here,
we
explore
comprehensive
role
tetrasulfide
(-SSSS-)
constructing
superior
DPNAs.
Compared
to
disulfide
bonds,
endow
with
superlative
self-assembly
stability,
prolonged
blood
circulation,
high
tumor
accumulation.
Notably,
ultra-high
reduction
responsivity
make
highly
selective
"tumor
bomb"
that
can
be
ignited
by
endogenous
reducing
agents
cells.
Furthermore,
present
an
"add
fuel
flames"
strategy
intensify
reductive
stress
at
sites
replenishing
exogenous
agents,
making
considerable
progress
inhibition.
This
work
elucidates
crucial
establishing
intelligent
DPNAs,
alongside
combination
methodology,
propelling
new
heights
potent
cancer
therapy.
Self-assembled
prodrug
nanoparticles
with
tumor-responsive
capacity
have
great
potential
in
tumor
visualization
and
treatment.
However,
the
nanoparticle
formulas
usually
contain
multiple
components,
especially
polymeric
materials,
which
result
various
issues.
Herein,
we
report
an
indocyanine
green
(ICG)-driven
assembly
of
paclitaxel
prodrugs
integrating
near-infrared
fluorescence
imaging
tumor-specific
chemotherapy.
By
feat
hydrophilic
merit
ICG,
dimer
could
form
more
uniformly
monodispersed
nanoparticles.
This
two-in-one
strategy
reinforces
complementary
advantages,
resulting
superior
behavior,
robust
colloidal
stability,
enhanced
accumulation
as
well
desirable
vivo
feedback
The
experiments
validated
activation
at
sites
evidenced
by
intensity,
potent
growth
suppression,
reduced
systemic
toxicity
compared
commercial
Taxol.
universality
ICG
potentiated
toward
photosensitizers
dyes
was
confirmed.
presentation
provides
deep
insight
into
feasibility
constructing
clinical-close
alternatives
for
improving
antitumor
efficacy.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Ноя. 24, 2022
Abstract
Sulfur
bonds,
especially
trisulfide
bond,
have
been
found
to
ameliorate
the
self-assembly
stability
of
homodimeric
prodrug
nanoassemblies
and
could
trigger
sensitive
reduction-responsive
release
active
drugs.
However,
antitumor
efficacy
with
single
reduction-responsivity
may
be
restricted
due
heterogeneous
tumor
redox
microenvironment.
Herein,
we
replace
middle
sulfur
atom
bond
an
oxidizing
tellurium
or
selenium
construct
dual-responsive
sulfur-tellurium-sulfur
sulfur-selenium-sulfur
hybrid
chalcogen
bonds.
The
exhibit
ultrahigh
dual-responsivity
both
oxidation
reduction
conditions,
which
effectively
address
Moreover,
promotes
prodrugs
by
providing
strong
intermolecular
forces
sufficient
steric
hindrance.
above
advantages
bridged
result
in
improved
docetaxel
satisfactory
safety.
exploration
bonds
drug
delivery
deepened
insight
into
development
prodrug-based
chemotherapy
heterogeneity,
thus
enriching
design
theory
nanomedicines.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(32), С. 22675 - 22688
Опубликована: Авг. 1, 2024
Redox-responsive
homodimer
prodrug
nanoassemblies
(RHPNs)
have
emerged
as
a
significant
technology
for
overcoming
chemotherapeutical
limitations
due
to
their
high
drug-loading
capacity,
low
excipient-associated
toxicity,
and
straightforward
preparation
method.
Previous
studies
indicated
that
α-position
disulfide
bond
bridged
RHPNs
exhibited
rapid
drug
release
rates
but
unsatisfactory
assembly
stability.
In
contrast,
γ-disulfide
showed
better
stability
rates.
Therefore,
designing
chemical
linkages
ensure
both
stable
remains
challenging.
To
address
this
paradox
of
in
RHPNs,
we
developed
carbon-spaced
double-disulfide
(CSDD)-bridged
(CSDD-RHPNs)
with
two
carbon-spaces.
Pilot
CSDD-RHPNs
carbon-spaces
enhanced
stability,
reduction-responsive
release,
improved
selective
toxicity
compared
α-/γ-position
single
RHPNs.
Based
on
these
findings,
four
six
were
designed
further
investigate
the
properties
CSDD-RHPNs.
These
excellent
ability,
safety,
prolonged
circulation.
Particularly,
displayed
best
antitumor
efficacy
4T1
B16–F10
tumor-bearing
mice.
CSDD
offer
novel
perspectives
rational
design
potentially
regarding
contradictory
ability
rate.
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2021,
Номер
16(6), С. 784 - 793
Опубликована: Июнь 6, 2021
Ferroptosis
is
a
new
mode
of
cell
death,
which
can
be
induced
by
Fenton
reaction-mediated
lipid
peroxidation.
However,
the
insufficient
H2O2
and
high
GSH
in
tumor
cells
restrict
efficiency
reaction-dependent
ferroptosis.
Herein,
self-supplying
peroxide
nanoreactor
was
developed
to
co-delivery
doxorubicin
(DOX),
iron
unsaturated
for
efficient
By
leveraging
coordination
effect
between
DOX
Fe3+,
trisulfide
bond-bridged
dimeric
prodrug
actively
loaded
into
core
lipids-rich
liposome
via
ion
gradient
method.
First,
Fe3+could
react
with
overexpressed
cells,
inducing
depletion
Fe2+generation.
Second,
cleavage
bond
could
also
consume
GSH,
released
induces
generation
H2O2,
would
generated
Fe2+in
step
one
induce
Third,
formed
Fe3+/Fe2+
couple
directly
catalyze
peroxidation
lipids
boost
reaction-independent
This
iron-prodrug
precisely
programs
multimodal
ferroptosis
integrating
depletion,
ROS
peroxidation,
providing
sights
cancer
therapy.
Advanced Materials,
Год журнала:
2023,
Номер
36(4)
Опубликована: Ноя. 21, 2023
Abstract
Homodimeric
prodrug
nanoassemblies
(HDPNs)
hold
promise
for
improving
the
delivery
efficiency
of
chemo‐drugs.
However,
key
challenge
lies
in
designing
rational
chemical
linkers
that
can
simultaneously
ensure
stability,
self‐assembly
and
site‐specific
activation
prodrugs.
The
“in
series”
increase
sulfur
atoms,
such
as
trisulfide
bond,
improve
assembly
stability
HDPNs
to
a
certain
extent,
but
limits
Herein,
trithiocarbonate
bond
(
─
SC(S)S
),
with
stable
“satellite‐type”
distribution
is
developed
via
insertion
central
carbon
atom
bonds.
effectively
addresses
existing
predicament
by
homodimeric
prodrugs
while
maintaining
on‐demand
bioactivation.
Furthermore,
inhibits
antioxidant
defense
system,
leading
up‐regulation
cellular
ROS
apoptosis
tumor
cells.
These
improvements
endow
vivo
longevity
specificity,
ultimately
enhancing
therapeutic
outcomes.
is,
therefore,
promising
overcoming
bottleneck
efficient
oncological
therapy.
Nano Letters,
Год журнала:
2024,
Номер
24(12), С. 3759 - 3767
Опубликована: Март 13, 2024
Prodrug
nanoassemblies
are
emerging
as
a
novel
drug
delivery
system
for
chemotherapy,
comprising
four
fundamental
modules:
module,
modification
response
and
surface
functionalization
module.
Among
these
modules,
is
an
essential
process
to
enhance
the
biocompatibility
stability
of
nanoassemblies.
Here,
we
selected
mitoxantrone
(MTO)
module
DSPE-PEG2K
develop
MTO
prodrug
We
systematically
evaluated
effect
ratios
(10%,
20%,
40%,
60%
prodrug,
WDSPE-mPEG2000/Wprodrug)
on
The
results
indicated
that
40%
NPs
significantly
improved
self-assembly
cellular
uptake
Compared
with
solution,
showed
better
tumor
specificity
pharmacokinetics,
resulting
in
potent
antitumor
activity
good
safety
profile.
These
findings
highlighted
pivotal
role
regulating
performance
cancer
treatment.
