Advanced Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 13, 2025
Abstract
The
power
of
drugs
lies
in
their
ability
to
reach
target
sites
and
remain
place
for
a
sufficient
duration
exert
therapeutic
effects.
However,
some
drugs,
lysosomal
phagocytosis
presents
ongoing
challenges.
In
this
study,
an
engineered
o
rganelles
v
isualization
d
rug‐delivery
s
ystem
(OVDS)
is
introduced
as
subcellular
drug
visualization
redistribution
framework
that
facilitates
the
movement
molecules
from
one
organelle,
specifically
lysosomes,
another,
such
mitochondria.
As
proof‐of‐concept
OVDS
developed
facilitate
translocation
10‐hydroxycamptothecin
(HCPT)
lysosomes
This
modification
HCPT
distribution
allows
evasion
lysosome‐mediated
resistance
cancer
cells.
Unlike
traditional
chemotherapeutic
approaches,
when
incorporated
into
(HCPT‐OVDS),
positive
charge
protonation,
thereby
enabling
escape
enter
Using
HCPT‐OVDS,
substantial
accumulation
achieved
at
HCPT‐resistant
cells,
with
up
70
±
6%
efficient
translocalization
12.8
fold
enhancement
cytotoxicity.
Overall,
HCPT‐OVDS
represents
innovative
engineering
spatial
offers
promising
solution
addressing
resistance.
ACS Nano,
Год журнала:
2024,
Номер
18(39), С. 26690 - 26703
Опубликована: Сен. 20, 2024
Herein,
we
constructed
a
paclitaxel
(PTX)
prodrug
(PA)
by
conjugating
PTX
with
acrylic
acid
as
cysteine-depleting
agent.
The
as-synthesized
PA
can
assemble
diacylphosphatidylethanolamine-PEG
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(31)
Опубликована: Июнь 17, 2024
Depot-type
drug
delivery
systems
are
designed
to
deliver
drugs
at
an
effective
rate
over
extended
period.
Minimizing
initial
"burst"
can
also
be
important,
especially
with
causing
systemic
toxicity.
Both
goals
challenging
small
hydrophilic
molecules.
The
of
molecules
such
as
the
ultrapotent
local
anesthetic
tetrodotoxin
(TTX)
exemplifies
both
challenges.
Toxicity
mitigated
by
conjugating
TTX
polymers
ester
bonds,
but
slow
hydrolysis
result
in
subtherapeutic
release.
Here,
we
developed
a
prodrug
strategy,
based
on
dynamic
covalent
chemistry
utilizing
reversible
reaction
between
diol
and
phenylboronic
acids.
These
polymeric
prodrugs
exhibited
encapsulation
efficiencies
exceeding
90
%
resulting
nanoparticles
showed
range
release
rates.
In
vivo
injection
sciatic
nerve
reduced
toxicity
produced
block
lasting
9.7±2.0
h,
comparison
1.6±0.6
h
from
free
TTX.
This
approach
could
used
co-deliver
dexamethasone,
which
prolonged
21.8±5.1
h.
work
emphasized
usefulness
for
depot-type
kinetics.
Angewandte Chemie,
Год журнала:
2024,
Номер
136(31)
Опубликована: Июнь 17, 2024
Abstract
Depot‐type
drug
delivery
systems
are
designed
to
deliver
drugs
at
an
effective
rate
over
extended
period.
Minimizing
initial
“burst”
can
also
be
important,
especially
with
causing
systemic
toxicity.
Both
goals
challenging
small
hydrophilic
molecules.
The
of
molecules
such
as
the
ultrapotent
local
anesthetic
tetrodotoxin
(TTX)
exemplifies
both
challenges.
Toxicity
mitigated
by
conjugating
TTX
polymers
ester
bonds,
but
slow
hydrolysis
result
in
subtherapeutic
release.
Here,
we
developed
a
prodrug
strategy,
based
on
dynamic
covalent
chemistry
utilizing
reversible
reaction
between
diol
and
phenylboronic
acids.
These
polymeric
prodrugs
exhibited
encapsulation
efficiencies
exceeding
90
%
resulting
nanoparticles
showed
range
release
rates.
In
vivo
injection
sciatic
nerve
reduced
toxicity
produced
block
lasting
9.7±2.0
h,
comparison
1.6±0.6
h
from
free
TTX.
This
approach
could
used
co‐deliver
dexamethasone,
which
prolonged
21.8±5.1
h.
work
emphasized
usefulness
for
depot‐type
kinetics.
Macromolecular Chemistry and Physics,
Год журнала:
2024,
Номер
225(9)
Опубликована: Фев. 12, 2024
Abstract
Tumor
microenvironment
heterogeneity
(TMH)
remains
a
challenge
in
cancer
treatment.
Nanocarrier
prodrugs
based
on
small‐molecular
drug
or
macromolecular
conjugates
emerge
as
an
efficient
approach
for
multidrug
delivery
at
tumor
sites
and
activating
the
by
endogenous
stimuli
resulting
from
TMH.
Herein,
redox/pH
dual‐sensitive
micelle
conjugated
is
developed
via
disulfide
linkage
with
naphthalimide‐based
prodrug
(PNA),
assigned
PDM
to
encapsulate
hypoxia‐activated
prodrug,
banoxantrone
(AQ4N),
combination
therapy.
These
micelles
have
several
interesting
features,
including
sufficiently
stable
less
release
under
physiological
conditions
dual
stimuli‐triggered
intracellular
release,
high
loading
content,
negligible
cytotoxicity.
More
importantly,
vitro
cytotoxicity
of
AQ4N‐loaded
exhibits
combinational
anticancer
efficacy
between
chemotherapy
PNA
AQ4N
hypoxic
conditions.
Moreover,
new
chemotherapeutic
displays
good
therapeutic
efficiency
fluorescent
properties,
which
can
be
used
monitoring
real
time.
This
study
not
only
offers
attractive
strategy
effective
traditional
chemotherapy,
but
also
provides
important
concept
develop
stimuli‐sensitive
nanoplatform
targeting
Pharmaceutical Research,
Год журнала:
2024,
Номер
41(8), С. 1725 - 1736
Опубликована: Июль 24, 2024
The
development
of
an
efficient,
multifunctional
drug
delivery
system
overcoming
different
obstacles
generally
associated
with
formulations,
including
the
poor
accumulation
active
principle
in
target
site
and
its
sustained
release
for
prolonged
time.
