Acetalated
dextran
(Ac-Dex)
nanoparticles
are
currently
of
immense
interest
due
to
their
sharp
pH-responsive
nature
and
high
biodegradability.
Ac-Dex
often
formulated
through
single-
or
double-emulsion
methods
utilizing
polyvinyl
alcohol
as
the
stabilizer.
The
emulsion
utilize
toxic
organic
solvents
such
dichloromethane
chloroform
require
multi-step
processing
form
stable
nanoparticles.
Here,
we
introduce
a
simple
flash
nanoprecipitation
(FNP)
approach
that
utilizes
confined
impinging
jet
mixer
non-toxic
solvent,
ethanol,
rapidly.
were
stabilized
using
nonionic
PEGylated
surfactants,
D-α-Tocopherol
polyethylene
glycol
succinate
(TPGS),
Pluronic
(F-127).
formed
FNP
highly
monodisperse
stably
encapsulated
wide
range
payloads,
including
hydrophobic,
hydrophilic,
macromolecules.
When
lyophilized,
TPGS
remained
for
at
least
one
year
with
greater
than
80%
payload
retention.
cells
achieved
intracellular
release
payloads
into
cytoplasm.
In
vivo
studies
demonstrated
predominant
biodistribution
in
liver,
lungs,
spleen
after
intravenous
administration.
Taken
together,
technique
allows
easy
fabrication
loading
can
precisely
environments
diverse
therapeutic
applications.
Acetalateddextran
be
F-127,
payloads.
Highly
created
simple,
scalable
technique,
which
impingement
mixer.
Nanorobotic
manipulation
to
access
subcellular
organelles
remains
unmet
due
the
challenge
in
achieving
intracellular
controlled
propulsion.
Intracellular
organelles,
such
as
mitochondria,
are
an
emerging
therapeutic
target
with
selective
targeting
and
curative
efficacy.
We
report
autonomous
nanorobot
capable
of
active
mitochondria-targeted
drug
delivery,
prepared
by
facilely
encapsulating
mitochondriotropic
doxorubicin-triphenylphosphonium
(DOX-TPP)
inside
zeolitic
imidazolate
framework-67
(ZIF-67)
nanoparticles.
The
catalytic
ZIF-67
body
can
decompose
bioavailable
hydrogen
peroxide
overexpressed
tumor
cells
generate
effective
movement
presence
TPP
cation.
This
nanorobot-enhanced
targeted
delivery
induces
mitochondria-mediated
apoptosis
mitochondrial
dysregulation
improve
vitro
anticancer
effect
suppression
cancer
cell
metastasis,
further
verified
vivo
evaluations
subcutaneous
model
orthotopic
breast
model.
unlocks
a
fresh
field
operation
organelle
access,
thereby
introducing
next
generation
robotic
medical
devices
organelle-level
resolution
for
precision
therapy.
Advanced Materials,
Год журнала:
2024,
Номер
36(18)
Опубликована: Янв. 15, 2024
Abstract
Mitochondria,
widely
known
as
the
energy
factories
of
eukaryotic
cells,
have
a
myriad
vital
functions
across
diverse
cellular
processes.
Dysfunctions
within
mitochondria
serve
catalysts
for
various
diseases,
prompting
widespread
demise.
Mounting
research
on
remedying
damaged
indicates
that
constitute
valuable
target
therapeutic
intervention
against
diseases.
But
less
clinical
practice
and
lower
recovery
rate
imply
limitation
traditional
drugs,
which
need
further
breakthrough.
Nanotechnology
has
approached
favorable
regiospecific
biodistribution
high
efficacy
by
capitalizing
excellent
nanomaterials
targeting
drug
delivery.
Mitochondria‐remedying
nanodrugs
achieved
ideal
effects.
This
review
elucidates
significance
in
cells
organs,
while
also
compiling
mortality
data
related
Correspondingly,
nanodrug‐mediate
strategies
applicable
mitochondria‐remedying
disease
are
detailed,
with
full
understanding
roles
dysfunction
advantages
nanodrugs.
In
addition,
future
challenges
directions
discussed.
conclusion,
this
provides
comprehensive
insights
into
design
development
nanodrugs,
aiming
to
help
scientists
who
desire
extend
their
fields
engage
interdisciplinary
subject.
Abstract
Emerging
evidence
has
demonstrated
the
significant
contribution
of
mitochondrial
metabolism
dysfunction
to
promote
cancer
development
and
progression.
Aberrant
expression
genome
(mtDNA)‐encoded
proteins
widely
involves
dysfunction,
targeted
regulation
their
can
be
an
effective
strategy
for
therapy,
which
however
is
challenged
due
protection
by
double
membrane.
Herein,
a
mitochondria‐targeted
RNAi
nanoparticle
(NP)
platform
breast
(BCa)
therapy
developed.
This
nanoplatform
composed
hydrophilic
polyethylene
glycol
(PEG)
shell,
hydrophobic
poly(2‐(diisopropylamino)ethyl
methacrylate)
(PDPA)
core,
charged‐mediated
complexes
mitochondria‐targeting
membrane‐penetrating
peptide
amphiphile
(MMPA)
small
interfering
RNA
(siRNA)
embedded
in
core.
After
tumor
accumulation
internalization
cells,
these
NPs
respond
endosomal
pH
expose
MMPA/siRNA
complexes,
specifically
transport
siRNA
into
mitochondria
down‐regulate
mtDNA‐encoded
protein
(e.g.,
ATP6
CYB).
More
importantly,
because
down‐regulation
suppress
ATP
production
enhance
reactive
oxygen
species
(ROS)
generation
induce
damage
mtDNA
leakage
tissues,
combinatorially
inhibit
growth
via
suppressing
repolarizing
tumor‐associated
macrophages
(TAMs)
tumor‐inhibiting
M1‐like
mtDNA.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(14), С. 11469 - 11487
Опубликована: Июль 9, 2024
Antibody-drug
conjugates
(ADCs)
comprise
antibodies,
cytotoxic
payloads,
and
linkers,
which
can
integrate
the
advantages
of
antibodies
small
molecule
drugs
to
achieve
targeted
cancer
treatment.
However,
ADCs
also
have
some
shortcomings,
such
as
non-negligible
drug
resistance,
a
low
therapeutic
index,
payload-related
toxicity.
Many
studies
focused
on
changing
composition
ADCs,
even
further
extended
concept
types
conjugated
by
replacing
in
with
peptides,
revolutionarily
introducing
peptide-drug
(PDCs).
This
Perspective
summarizes
current
research
status
PDCs
highlights
structural
innovations
ADC
components.
In
particular,
are
regarded
next
generation
potential
after
challenges
analyzed.
Our
aim
is
offer
fresh
insights
for
efficient
design
expedited
development
innovative
drugs.
Advanced Drug Delivery Reviews,
Год журнала:
2024,
Номер
207, С. 115195 - 115195
Опубликована: Фев. 5, 2024
Enhanced
targeting
approaches
will
support
the
treatment
of
diseases
associated
with
dysfunctional
mitochondria,
which
play
critical
roles
in
energy
generation
and
cell
survival.
Obstacles
to
mitochondria-specific
include
presence
distinct
biological
barriers
need
pass
through
(or
avoid)
various
internalization
mechanisms.
A
range
studies
have
reported
design
mitochondrially-targeted
nanomedicines
that
navigate
complex
routes
required
influence
mitochondrial
function;
nonetheless,
a
significant
journey
lies
ahead
before
become
suitable
for
clinical
use.
Moving
swiftly
forward
require
safety
studies,
vivo
assays
confirming
effectiveness,
methodologies
validate
mitochondria-targeted
nanomedicines'
subcellular
location/activity.
From
nanomedicine
standpoint,
we
describe
involved
(from
administration
arrival
within
mitochondria),
features
influencing
rational
design,
techniques
used
identify/validate
successful
targeting.
Overall,
rationally-designed
mitochondria-targeted-based
hold
great
promise
precise
therapeutic
delivery.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(50)
Опубликована: Авг. 15, 2024
Abstract
New
generation
of
nanomaterials
with
organelle‐level
precision
provide
significant
promise
for
targeted
attacks
on
mitochondria,
exhibiting
remarkable
therapeutic
potency.
Here,
we
report
a
novel
amphiphilic
phenolic
polymer
(PF)
the
mitochondria‐targeted
photodynamic
therapy
(PDT),
which
can
trigger
excessive
mitochondrial
DNA
(mtDNA)
damage
by
synergistic
action
oxidative
stress
and
furan‐mediated
cross‐linking.
Moreover,
units
PF
enable
further
self‐assembly
Mn
2+
via
metal‐phenolic
coordination
to
form
nanomaterial
(PFM).
We
focus
activation
cGAS‐STING
pathway
tumor‐derived
mtDNA
in
tumor‐associated
macrophages
(TAMs),
subsequently
repolarizing
M2‐like
TAMs
M1
phenotype.
highlight
that
PFM
facilitates
cGAS‐STING‐dependent
immunity
at
organelle
level
potent
antitumor
efficacy.
International Journal of Nanomedicine,
Год журнала:
2025,
Номер
Volume 20, С. 1899 - 1920
Опубликована: Фев. 1, 2025
Background:
The
development
of
selective
formulations
able
to
target
and
kill
tumor
cells
without
the
application
external
energy
has
shown
great
promise
for
anti-tumor
therapy.
Methods:
Here,
we
report
a
"nanobomb"
that
explosively
increases
Ca
content
within
cells.
It
can
selectively
release
2+
generate
H
2
O
in
microenvironment
(TME)
by
acid-triggered
degradation
two-layer
protective
shell
(ie,
unlocking
"double-lock").
This
material,
termed
CaO
@ZIF8:CUR@PAA,
comprises
core
coated
with
ZIF-8
framework,
which
was
then
loaded
curcumin
(CUR)
again
polyacrylic
acid
(PAA).
Results:
Under
slightly
acidic
conditions
TME,
PAA
(first
lock)
breaks
down
first
exposing
@ZIF8
CUR
inside
cell.
Then,
ZIF8
(second
is
degraded
response
deposit
,
.
promote
from
endoplasmic
reticulum
cytoplasm,
inhibit
outflow
accumulates
large
amount
intracellularly
together
exogenous
(calcium
storms).
powerful
calcium
storm
causes
mitochondrial
dysfunction.
presence
further
oxidative
damage
cell
membranes
mitochondria
where
intracellular
ROS
production
far
exceeds
clearance.
@ZIF8:CUR@PAA
NPs
induce
S
cycle
arrest
apoptosis
multiplication
growth.
Oxidative
damage-triggered
immunogenic
death
(ICD)
turn
leads
polarization
macrophages
M1
phenotype,
inducing
inhibiting
proliferation
metastasis.
Discussion:
two-step
nanoplatform
therapeutic
modality
combines
damage.
mode
triggers
leading
ICD
material
induces
blockade
during
treatment
proliferation.
Robust
vitro
vivo
data
demonstrate
efficacy
this
approach
as
an
anticancer
platform,
paving
way
nanomaterials
immune-triggered
cancer
Highlights:
-
A
new
accumulation
plays
role
activate
antitumor
immunity.-
Double-locked
structure
slows
premature
decomposition
.-
platform
allows
accumulate
cells.-
dysfunction,
apoptosis,
macrophage
polarization.-
Potent
effects
are
seen
both
vivo.
Keywords:
Calcium
ion
load,
controlled-release
nanomaterials,
shell,
pH
responsive
drug
release,
reactive
oxygen
species,
anti-cancer
