ABSTRACT
Myotonic
dystrophy
type
1
(DM1)
is
considered
a
progeroid
disease
(i.e.,
causing
premature
aging).
This
hypervariable
affects
multiple
systems,
such
as
the
musculoskeletal,
central
nervous,
gastrointestinal,
and
others.
Despite
advances
in
understanding
underlying
pathogenic
mechanism
of
DM1,
numerous
gaps
persist
our
understanding,
hindering
elucidation
heterogeneity
severity
its
symptoms.
Accumulating
evidence
indicates
that
toxic
intracellular
RNA
accumulation
associated
with
DM1
triggers
cellular
senescence.
These
cells
are
state
irreversible
cell
cycle
arrest
secrete
cocktail
cytokines,
referred
to
senescence‐associated
secretory
phenotype
(SASP),
can
have
harmful
effects
on
neighboring
more
broadly.
We
hypothesize
senescence
contributes
pathophysiology
clearance
senescent
promising
therapeutic
approach
for
DM1.
will
discuss
potential
different
senotherapeutic
drugs,
especially
senolytics
eliminate
cells,
senomorphics
reduce
SASP
expression.
Advanced NanoBiomed Research,
Год журнала:
2024,
Номер
4(4)
Опубликована: Фев. 6, 2024
Intracellular
assemblies
play
vital
roles
in
maintaining
cellular
functions
through
structural
recognition‐mediated
interactions.
The
introduction
of
artificial
structures
has
garnered
substantial
interest
modulating
via
activation/inhibition
interactions
with
biomacromolecules.
However,
the
uptake
these
high‐molecular‐weight
may
limit
their
performance.
Recently,
intracellular
chemical‐reaction‐induced
self‐assembly
emerged
as
a
promising
strategy
for
generating
situ
nanostructures
biofunctionalities
interacting
This
approach
addresses
challenge
synthetic
reactions
occurring
complex
environments
by
utilizing
diverse
chemical
that
respond
to
endogenous
and
exogenous
stimuli.
review
provides
an
overview
latest
advancements
techniques.
It
focuses
on
responsiveness
specific
conditions,
such
redox
overexpressed
enzymes.
Additionally,
initiation
stimuli,
including
reagents
irradiation
is
explored.
Polymerization‐induced
hydrophobicity
highlighted,
leading
into
micro‐/nanostructures.
These
processes
contribute
construction
materials
morphologies,
offering
versatile
functionalities
biological
applications.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 26, 2024
Cellular
senescence
is
a
significant
risk
factor
for
aging
and
age-related
diseases
(ARD).
The
canonical
senolytics
Dasatinib
Quercetin
(DQ)
have
shown
promise
in
clearing
senescent
cells
(SnCs);
however,
the
lack
of
selectivity
poses
challenge
achieving
optimal
outcomes.
Despite
recent
occurrence
nanomaterial-based
approaches
targeting
SnCs,
limited
therapeutic
effects,
potential
toxicity
still
remain
major
concern.
Herein,
"double
locks-like"
nanoplatform
developed
that
integrated
Galactan
coating
mesoporous
polydopamine
to
encase
senolytic
drug
DQ.
By
this
way,
DQ
only
released
SnCs
are
featured
with
higher
levels
β-galactosidase
(β-gal)
low
PH.
Additionally,
nanoparticles
equipped
2,2,6,6-Tetramethylpiperidine-1-oxyl
(Tempo)
gain
enhanced
photothermal
converting
potential.
Consequently,
synthesized
nanosenolytics
demonstrate
remarkable
specificity
efficacy
eradicating
accordingly
reverse
pulmonary
fibrosis
mice
without
affecting
normal
tissues.
Upon
exposure
near-infrared
(NIR)
light,
efficiently
remove
tumor
inducted
by
chemotherapy,
thereby
hindering
outgrowth
metastasis
or
breast
cancer.
Collectively,
present
study
develops
an
"On/Off"
switchable
response
produces
more
safe,
efficient,
feasible
way
delay
alleviate
age-associated
diseases.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
14(4)
Опубликована: Ноя. 6, 2024
To
address
the
issue
of
nonspecific
biodistribution
a
chemotherapeutic
drug,
stable
[2]pseudorotaxane
complexes
(PK@CAOPP
and
PR@CAOPP)
are
used
to
demonstrate
proof
concept.
Cationic
-PPh3
+
moiety
in
CAOPP
allows
specific
localization
PK@CAOPP/
PR@CAOPP
mitochondrial
membrane
(MM).
Electrostatic
interaction
between
cationic
LysinePK
or
ArgininePR
negatively
charged
phosphoesterCAOPP
functionality
favours
strong
adduct
formation.
The
ALP-induced
hydrolytic
cleavage
phosphoester
cancer
cells
triggers
dephosphorylation
releases
PK/
PR
from
PK@CAOPP/PR@CAOPP.
PK
PR,
derived
Phe-Phe
dipeptide,
formed
fibril-like
molecular
aggregates
MM
induce
dysfunction,
depolarization,
ROS
generation
apoptotic
MCF7
cell
death.
Such
phenomena
were
not
observed
ALP-negative
HEK293
normal
cells.
These
propositions
confirmed
through
control
studies
using
NBDK
PE,
other
guest
molecules.
Smaller
size
inclusion
short
peptides
(PK
PR)
within
hydrophobic
interior
CAOPP,
attributed
their
stability
blood
serum.
Thus,
we
have
demonstrated
use
supramolecular
adducts
as
potential
therapeutic
option
for
treating
without
affecting
healthy
efficacy
was
also
established
with
an
in-vivo
tumour
xenograft
model
Balb/c
nude
mice.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Recently,
targeted
protein
degradation
(TPD)
strategies
have
emerged
as
a
promising
solution
to
tackle
undruggable
proteins.
While
most
TPD
target
intracellular
proteins,
limited
options
exist
for
targeting
extracellular
or
membrane
Herein,
cancer
specific
carbonic
anhydrase
IX
(CAIX)-targeting
supramolecular
nanofibrous
lysosome-targeting
chimeras
(Supra-LYTAC)
is
reported.
Two
self-assembling
amphiphilic
peptides
are
synthesized:
one
that
interacts
with
the
of
interest
(POI),
and
another
mediates
lysosomal
endocytosis
by
cancer-specific
enzyme.
Notably,
these
two
co-assemble
into
nanofibers
capable
cells
in
spatiotemporal
manner.
Through
dynamic
multivalent
binding,
ternary
complex
form
(supramolecular
chimeric
nanostructure;
CAIX-nanofiber-POI),
which
undergoes
internalization
lysosomes
where
POI
degraded
through
catalytic
activity.
This
study
demonstrates
potential
approaches
expand
scope
LYTAC
technology,
offering
new
opportunities
designing
future.
