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.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(11), С. 4683 - 4716
Опубликована: Сен. 2, 2024
About
40%
of
approved
drugs
and
nearly
90%
drug
candidates
are
poorly
water-soluble
drugs.
Low
solubility
reduces
the
drugability.
Effectively
improving
bioavailability
is
a
critical
issue
that
needs
to
be
urgently
addressed
in
development
application.
This
review
briefly
introduces
conventional
solubilization
techniques
such
as
solubilizers,
hydrotropes,
cosolvents,
prodrugs,
salt
modification,
micronization,
cyclodextrin
inclusion,
solid
dispersions,
details
crystallization
strategies,
ionic
liquids,
polymer-based,
lipid-based,
inorganic-based
carriers
bioavailability.
Some
most
commonly
used
carrier
materials
for
presented.
Several
using
summarized.
Furthermore,
this
summarizes
mechanism
each
technique,
reviews
latest
research
advances
challenges,
evaluates
potential
clinical
translation.
could
guide
selection
approach,
dosage
form,
administration
route
Moreover,
we
discuss
several
promising
attracting
increasing
attention
worldwide.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(16)
Опубликована: Фев. 7, 2024
Abstract
High
reactive
oxygen
species
(ROS)
levels
in
tumor
microenvironment
(TME)
impair
both
immunogenic
cell
death
(ICD)
efficacy
and
T
activity.
Furthermore,
escapes
immunosurveillance
via
programmed
death‐1/programmed
ligand‐1
(PD‐L1)
signal,
the
insufficient
intracellular
hydrogen
peroxide
weakens
ferroptosis
efficacy.
To
tackle
above
issues,
a
glutathione
(GSH)/ROS/pH
triple‐responsive
prodrug
nanomedicine
that
encapsulates
Fe
2
O
3
nanoparticle
electrostatic
interaction
is
constructed
for
magnetic
resonance
imaging
(MRI)‐guided
multi‐mode
theranostics
with
chemotherapy/ferroptosis/immunotherapy.
The
diselenide
bond
consumes
ROS
TME
to
increase
cells
ICD
efficacy,
cleavage
of
which
facilitates
PD‐L1
antagonist
D
peptide
release
block
immune
checkpoint.
After
internalization,
released
acidic
endosome
MRI
simultaneously
lipid
peroxides
generation
ferroptosis.
Doxorubicin
cleaved
from
polymers
condition
high
GSH
level
accompanied
by
ICD,
potentiates
NADPH
oxidase
mediated
H
self‐generation.
In
vivo
results
indicate
nanoplatform
strengthens
induces
cytotoxic
lymphocytes
proliferation,
inhibits
4T1
regression
metastasis,
prolongs
survival
median.
all,
new
strategy
proposed
strengthening
activity
cascade
as
well
checkpoint
blockade
effective
immunotherapy.
Nano Letters,
Год журнала:
2024,
Номер
24(11), С. 3548 - 3556
Опубликована: Март 8, 2024
After
spinal
cord
injury
(SCI),
successive
systemic
administration
of
microtubule-stabilizing
agents
has
been
shown
to
promote
axon
regeneration.
However,
this
approach
is
limited
by
poor
drug
bioavailability,
especially
given
the
rapid
restoration
blood–spinal
barrier.
There
a
pressing
need
for
long-acting
formulations
in
treating
SCI.
Here,
we
conjugated
antioxidant
idebenone
with
paclitaxel
create
heterodimeric
paclitaxel–idebenone
prodrug
via
an
acid-activatable,
self-immolative
ketal
linker
and
then
fabricated
it
into
chondroitin
sulfate
proteoglycan-binding
nanomedicine,
enabling
retention
within
at
least
2
weeks
notable
enhancement
hindlimb
motor
function
regeneration
after
single
intraspinal
administration.
Additional
investigations
uncovered
that
can
suppress
activation
microglia
neuronal
ferroptosis,
thereby
amplifying
therapeutic
effect
paclitaxel.
This
prodrug-based
nanomedicine
simultaneously
accomplishes
neuroprotection
regeneration,
offering
promising
strategy
Materials Advances,
Год журнала:
2024,
Номер
5(11), С. 4634 - 4659
Опубликована: Янв. 1, 2024
This
review
focuses
on
updates
regarding
a
broad
spectrum
of
fabrication
advances
and
applications
in
the
field
prodrug-based
nanotechnologies
multiple
cancer
therapeutic
strategies
response
to
tumor
microenvironment.
ACS Central Science,
Год журнала:
2024,
Номер
10(7), С. 1371 - 1382
Опубликована: Июнь 21, 2024
Radiotherapy
is
commonly
used
to
treat
cancer,
and
localized
energy
deposited
by
radiotherapy
has
the
potential
chemically
uncage
prodrugs;
however,
it
been
challenging
demonstrate
prodrug
activation
that
both
sustained
in
vivo
truly
tumors
without
affecting
off-target
tissues.
To
address
this,
we
developed
a
series
of
novel
phenyl-azide-caged,
radiation-activated
chemotherapy
drug-conjugates
alongside
computational
framework
for
understanding
corresponding
pharmacokinetic
pharmacodynamic
(PK/PD)
behaviors.
We
especially
focused
on
an
albumin-bound
monomethyl
auristatin
E
(MMAE)
found
blocked
tumor
growth
mice,
delivered
130-fold
greater
amount
activated
drug
irradiated
versus
unirradiated
tissue,
was
7.5-fold
more
efficient
than
non
prodrug,
showed
no
appreciable
toxicity
compared
free
or
cathepsin-activatable
drugs.
These
data
guided
modeling
action,
which
indicated
extended
pharmacokinetics
can
improve
cumulative
activation,
payloads
with
low
vascular
permeability
diffusivity
particularly
patients
receiving
daily
treatments
conventional
weeks.
This
work
thus
offers
quantitative
PK/PD
proof-of-principle
experimental
demonstration
how
extending
circulation
its
activity
vivo.
