Fundamental Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 1, 2024
Mitoxantrone
(MTO)
is
an
anthraquinone
antitumor
drug
with
potent
therapeutic
benefits.
However,
its
clinical
application
restricted
by
the
severe
side
effects
stemming
from
poor
tumor
selectivity.
In
this
study,
MTO
and
cholesterol
(CLS)
were
conjugated
via
a
tumor-selective
disulfide
bond
to
obtain
MTO-SS-CLS
prodrug.
Interestingly,
could
self-assemble
into
uniform
nanoassemblies,
addition
of
DSPE-PEG2K
significantly
improved
self-assembly
behavior
stability.
Moreover,
compared
solutions,
bond-bridged
nanoassemblies
exhibited
heightened
selectivity
pharmacokinetic
properties.
addition,
prodrug
tolerated
dose
safety
without
compromising
effect.
This
research
enriches
pharmaceutical
paves
way
for
extensive
application.
Langmuir,
Год журнала:
2024,
Номер
40(21), С. 11098 - 11105
Опубликована: Май 13, 2024
Disulfide
bonding
has
attracted
intense
interest
in
the
tumor
intracellular
microenvironment-activated
drug
delivery
systems
(DDSs)
last
decades.
Although
various
molecular
structures
of
redox-responsive
disulfide-containing
DDSs
have
been
developed,
no
investigation
was
reported
on
effect
aggregation
structures.
Here,
pH/GSH
dual-triggered
release
investigated
with
simplest
doxorubicin-based
self-delivery
system
(DSDS),
disulfide/α-amide-bridged
doxorubicin
dimeric
prodrug
(DDOX),
as
a
model.
By
fast
precipitation
or
slow
self-assembly,
DDOX
nanoparticles
were
obtained.
With
similar
diameters,
they
exhibited
different
releases,
demonstrating
The
π–π
stacking
degrees
revealed
by
UV–vis,
fluorescence,
and
BET
analysis
nanoparticles.
between
its
activated
products
also
explored
simulation
approach.
finding
opens
new
ideas
design
high-performance
for
future
precise
treatment.
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2022,
Номер
17(2), С. 241 - 252
Опубликована: Фев. 27, 2022
PEGylation
has
been
widely
used
to
improve
the
pharmacokinetic
properties
of
prodrug
self-assembled
nanoparticles
(prodrug-SANPs).
However,
impacts
amount
PEG
on
self-assemble
stability,
cellular
uptake,
pharmacokinetics,
and
antitumor
efficacy
prodrug-SANPs
are
still
unknown.
Herein,
selenoether
bond
bridged
docetaxel
dimeric
was
synthesized
as
model
prodrug.
Five
were
designed
by
using
different
mass
ratios
prodrugs
(Wprodrug/WDSPE-mPEG2000
=
10:0,
9:1,
8:2,
7:3
6:4),
defined
Pure
drug
NPs,
9:1NPs,
8:2NPs,
NPs
6:4
respectively.
Interestingly,
8:2
formed
most
compact
nanostructure,
thus
improving
stability
pharmacokinetics
behavior.
In
addition,
difference
these
in
uptake
investigated,
influence
cytotoxicity
also
clarified
details.
The
exhibited
much
better
than
other
even
commercial
product.
Our
findings
demonstrated
pivotal
role
prodrug-SANPs.
Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
155, С. 113707 - 113707
Опубликована: Сен. 16, 2022
Due
to
the
complexity
and
particularity
of
cancer
cell
microenvironments,
redox
responsive
drug
delivery
systems
(DDSs)
for
therapy
have
been
extensively
explored.
Compared
with
widely
reported
treatment
based
on
disulfide
bonds,
diselenide
bonds
better
properties
greater
anticancer
efficiency.
In
this
review,
significance
application
in
DDSs
are
summarized,
stimulation
sensitivity
is
comprehensively
reported.
The
potential
prospects
next-generation
discussed.
Nano Letters,
Год журнала:
2023,
Номер
23(8), С. 3549 - 3557
Опубликована: Апрель 13, 2023
Prodrug-based
nanoassemblies
have
been
developed
to
solve
the
bottlenecks
of
chemotherapeutic
drugs.
The
fabricated
prodrugs
usually
consist
active
drug
modules,
response
and
modification
modules.
Among
three
modules
play
a
vital
role
in
controlling
intelligent
release
at
tumor
sites.
Herein,
various
locations
disulfide
bond
linkages
were
selected
as
construct
Docetaxel
(DTX)
prodrugs.
Interestingly,
small
structural
difference
caused
by
length
endowed
corresponding
prodrug
with
unique
characteristic.
α-DTX-OD
nanoparticles
(NPs)
possessed
advantages
high
redox-responsiveness
due
their
shortest
linkages.
However,
they
too
sensitive
retain
intact
structure
blood
circulation,
leading
severe
systematic
toxicity.
β-DTX-OD
NPs
significantly
improved
pharmacokinetics
DTX
but
may
induce
damage
liver.
In
comparison,
γ-DTX-OD
longest
greatly
ameliorated
delivery
efficiency
well
DTX's
tolerance
dose.
Acta Pharmaceutica Sinica B,
Год журнала:
2023,
Номер
14(3), С. 1400 - 1411
Опубликована: Сен. 30, 2023
The
self-assembly
prodrugs
are
usually
consisted
of
drug
modules,
activation
and
assembly
modules.
Keeping
the
balance
between
efficacy
safety
by
selecting
suitable
modules
remains
a
challenge
for
developing
prodrug
nanoassemblies.
This
study
designed
four
docetaxel
(DTX)
using
disulfide
bonds
as
different
lengths
branched-chain
fatty
alcohols
(C16,
C18,
C20,
C24).
determined
ability
affected
modules'
sensitivity.
extension
carbon
chains
improved
prodrugs'
pharmacokinetic
behavior
while
reducing
cytotoxicity
increased
cumulative
toxicity.
use
C20
can
safety.
These
results
provide
great
reference
rational
design
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 Applied Materials & Interfaces,
Год журнала:
2021,
Номер
13(39), С. 46291 - 46302
Опубликована: Сен. 24, 2021
The
current
clinical
performance
of
chemotherapy
is
far
from
satisfactory,
greatly
limited
by
insufficient
delivery
efficacy
and
serious
systemic
side
effects.
Dimeric
prodrug
systems
are
emerging
as
valuable
strategies
for
boosting
the
antitumor
outcome.
Here,
dimeric
paclitaxel
prodrugs
were
synthesized
with
different
bridged
linkers,
formed
nanoparticles
possessed
excellent
colloidal
stability
ultrahigh
drug
content.
diselenide
bond
containing
could
respond
to
a
redox-heterogeneous
intracellular
microenvironment
on-demand
release
subsequently
show
selective
cytotoxicity
toward
tumor
cells
against
normal
cells.
Furthermore,
optimal
carrier
materials
screened
out
according
their
contribution
on
stability,
endocytosis,
cytotoxicity,
biodistribution,
efficacy.
Compared
DSPE-PEG,
human
serum
albumin,
Fe-tannic
acid-based
complex,
F127
anchored
nanoformulations
exhibited
preferential
accumulation
potent
anticancer
effect.
Our
present
work
provides
deep
insight
into
development
advanced
comprehensive
advantages
enhancing
cancer
therapy.
