Journal of Inorganic Biochemistry,
Год журнала:
2024,
Номер
254, С. 112505 - 112505
Опубликована: Фев. 15, 2024
Platinum-based
anticancer
drugs,
while
potent,
are
associated
with
numerous
and
severe
side
effects.
Hyperthermia
therapy
is
an
effective
adjuvant
in
treatment,
however,
clinically
used
platinum
drugs
have
not
been
optimised
for
combination
hyperthermia.
The
derivatisation
of
existing
appropriately
chosen
thermoresponsive
moieties
results
being
activated
only
at
the
heated
site.
Perfluorinated
chains
varying
lengths
were
installed
on
carboplatin,
a
approved
drug,
leading
to
successful
synthesis
series
mono-
di-
substituted
platinum(IV)
carboplatin
prodrugs.
Some
these
complexes
display
relevant
thermosensitivity
ovarian
cancer
cell
lines,
i.e.,
inactive
37
°C
having
comparable
activity
under
mild
hyperthermia
(42
°C).
Nuclear
magnetic
resonance
spectroscopy
mass
spectrometry
indicated
that
likely
active
platinum(II)
agent
upon
reduction
cyclic
voltammetry
revealed
length
fluorinated
alkyl
chain
has
strong
influence
rate
formation,
regulating
subsequent
cytotoxicity.
ACS Applied Bio Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 2, 2024
Ultrasound
has
gained
prominence
in
biomedical
applications
due
to
its
noninvasive
nature
and
ability
penetrate
deep
tissue
with
spatial
temporal
resolution.
The
burgeoning
field
of
ultrasound-responsive
prodrug
systems
exploits
the
mechanical
chemical
effects
ultrasonication
for
controlled
activation
prodrugs.
In
polymer
mechanochemistry,
materials
scientists
exploit
sonomechanical
effect
acoustic
cavitation
mechanochemically
activate
force-sensitive
On
other
hand,
researchers
sonodynamic
therapy
adopt
fundamentally
distinct
methodologies,
utilizing
sonochemical
(e.g.,
generation
reactive
oxygen
species)
ultrasound
presence
sonosensitizers
induce
transformations
that
This
cross-disciplinary
review
comprehensively
examines
these
two
divergent
yet
interrelated
approaches,
both
which
originated
from
cavitation.
It
highlights
molecular
design
strategies
potential
diverse
therapeutic
contexts,
chemotherapy
immunotherapy
gene
methods,
discusses
future
directions
this
rapidly
advancing
domain.
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.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(24), С. 16546 - 16567
Опубликована: Дек. 12, 2023
Time-
and
space-resolved
drug
delivery
is
highly
demanded
for
cancer
treatment,
which,
however,
can
barely
be
achieved
with
a
traditional
prodrug
strategy.
In
recent
years,
the
strategy
based
on
bioorthogonal
bond
cleavage
chemistry
has
emerged
advantages
of
high
temporospatial
resolution
over
activation
homogeneous
irrespective
individual
heterogeneity.
past
five
tremendous
progress
been
witnessed
in
this
field
one
such
entering
Phase
II
clinical
trials.
This
Perspective
aims
to
highlight
these
new
advances
(2019–2023)
critically
discuss
their
pros
cons.
addition,
remaining
challenges
potential
strategic
directions
future
will
also
included.
Abstract
The
clinical
approval
of
platinum‐based
drugs
has
prompted
the
development
novel
metallo‐complexes
during
last
several
decades,
while
severe
problems,
especially
for
poor
water
solubility,
drug
resistance
and
toxicity
in
patients,
greatly
hindered
trials
curative
efficacy.
To
address
these
issues,
concept
metallo‐prodrugs
been
proposed
oncology.
Some
stimuli‐activable
provide
new
insights
designing
preparing
site‐specific
prodrugs
with
maximized
therapeutic
efficacy
negligible
unfavorable
by‐effects.
In
this
review,
recent
progress
past
20
years
overviewed,
where
endogenous
exogenous
stimuli
have
involved.
Typical
examples
smart
are
discussed
regarding
to
their
molecular
structure,
activation
mechanism,
promising
biomedical
applications.
end,
challenges
future
perspectives
discussed.
Gene
therapy
and
sonodynamic
therapy,
as
emerging
treatment
methods,
have
great
potential
in
cancer
treatment.
However,
there
are
significant
challenges
the
vivo
delivery
of
genes
sonosensitizers
during
process,
which
ultimately
affects
therapeutic
outcome.
In
this
study,
an
ultrasound-sensitive
targeted
liposome
nanoparticle
system
(MLip
Abstract
Platinum(II)
complexes
are
used
in
approximately
50%
of
chemotherapeutic
treatments
worldwide.
Despite
their
undoubtful
clinical
success,
these
compounds
associated
with
severe
side
effects
and
poor
tumor
selectivity.
To
overcome
drawbacks,
the
development
platinum(IV)
molecular
prodrugs
nanoparticle
formulations
that
remain
stable
therapeutically
inactive
a
biological
environment,
but
could
be
quickly
reduced
into
active
analogs
through
specific
trigger
have
been
thought.
Within
this
article,
mechanisms
for
chemical
photophysical
triggers
activation
critically
reviewed.
