bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 20, 2023
ABSTRACT
Messenger
RNA
(mRNA)
has
emerged
as
an
attractive
therapeutic
molecule
for
a
plethora
of
clinical
applications.
For
in
vivo
functionality,
mRNA
therapeutics
require
encapsulation
into
effective,
stable,
and
safe
delivery
systems
to
protect
the
cargo
from
degradation
reduce
immunogenicity.
Here,
bioengineering
platform
efficient
loading
functional
using
bionormal
nanoparticles,
Extracellular
Vesicles
(EVs),
is
established
by
expressing
highly
specific
RNA-binding
domain
fused
CD63
EV
producer
cells
stably
target
mRNA.
The
additional
combination
with
fusogenic
endosomal
escape
moiety,
VSVg,
enables
at
doses
substantially
lower
than
currently
used
clinically
synthetic
lipid-based
nanoparticles.
Importantly,
application
EVs
loaded
effective
cancer
immunotherapy
proves
aggressive
melanoma
mouse
model.
This
technology
addresses
substantial
drawbacks
associated
EV-based
nucleic
acid
leap
forward
Graphical
Abstract
(Figure
created
BioRender)
International Journal of Oral Science,
Год журнала:
2024,
Номер
16(1)
Опубликована: Апрель 16, 2024
Abstract
Accumulating
evidence
has
demonstrated
that
apoptotic
vesicles
(apoVs)
derived
from
mesenchymal
stem
cells
(MSCs;
MSC-apoVs)
are
vital
for
bone
regeneration,
and
possess
superior
capabilities
compared
to
MSCs
other
extracellular
(such
as
exosomes).
The
osteoinductive
effect
of
MSC-apoVs
is
attributed
their
diverse
contents,
especially
enriched
proteins
or
microRNAs
(miRNAs).
To
optimize
osteoinduction
activity,
it
necessary
determine
the
unique
cargo
profiles
MSC-apoVs.
We
previously
established
protein
landscape
identified
specific
However,
features
functions
miRNAs
in
unclear.
In
this
study,
we
MSCs,
MSC-apoVs,
MSC-exosomes
two
types
MSC.
generated
a
map
seven
specifically
MSC-exosomes,
which
classified
apoV-specific
miRNAs.
Among
these
miRNAs,
hsa-miR-4485-3p
was
most
abundant
stable.
Next,
explored
its
function
apoV-mediated
osteoinduction.
Unexpectedly,
inhibited
osteogenesis
promoted
adipogenesis
by
targeting
AKT
pathway.
Tailored
apoVs
with
downregulated
exhibited
greater
on
regeneration
than
control
apoVs.
Like
releasing
brake,
acquired
more
powerful
summary,
miRNA
cargos,
including
tailored
high
promising
apoV-based
therapies
regeneration.
JACS Au,
Год журнала:
2024,
Номер
4(6), С. 2381 - 2392
Опубликована: Май 30, 2024
Extracellular
vesicles
(EVs)
are
naturally
occurring
secreted
by
cells
that
can
transport
cargo
between
cells,
making
them
promising
bioactive
nanomaterials.
However,
due
to
the
complex
and
heterogeneous
biological
characteristics,
a
method
for
robust
EV
manipulation
efficient
delivery
is
still
lacking.
Here,
we
developed
novel
class
of
extracellular
vesicle
spherical
nucleic
acid
(EV-SNA)
nanostructures
with
scalability,
programmability,
cellular
delivery.
EV-SNA
was
constructed
through
simple
hydrophobic
coassembly
natural
EVs
cholesterol-modified
oligonucleotides
be
stable
1
month
at
room
temperature.
Based
on
programmable
shells,
respond
AND
logic
gates
achieve
assembly
manipulation.
Importantly,
from
wide
range
sources
EV,
enhancing
capability
nearly
10–20
times.
Compared
artificial
liposomal
SNA,
endogenous
exhibited
better
biocompatibility
more
effective
antisense
in
hard-to-transfect
primary
stem
cells.
Additionally,
deliver
functional
immune
regulation.
As
material
form,
may
provide
modular
framework
paradigm
EV-based
applications
drug
delivery,
disease
treatment,
nanovaccines,
other
fields.
Journal of Extracellular Vesicles,
Год журнала:
2024,
Номер
13(7)
Опубликована: Июль 1, 2024
Abstract
Extracellular
vesicles
(EVs)
have
emerged
as
promising
biomaterials
for
the
treatment
of
different
disease.
However,
only
handful
types
EVs
with
clinical
transformation
potential
been
reported
to
date,
and
their
preparation
on
a
large
scale
under
biosafety‐controlled
conditions
is
limited.
In
this
study,
we
characterize
novel
type
EV
application
potential:
dehydration‐induced
extracellular
(DIMVs).
DIMV
micron‐diameter
cell
vesicle
that
contains
more
bioactive
molecules,
such
proteins
RNA,
but
not
DNA,
than
previously
vesicles.
The
extraordinarily
straightforward,
which
possesses
high
level
biosafety,
protein
utilization
ratio
roughly
600
times
greater
naturally
secreted
EVs.
Additional
experiments
demonstrate
viability
pre‐
or
post‐isolation
modification,
including
gene
editing,
nucleic
acid
encapsulation
surface
anchoring,
size
adjustment.
Finally,
animal
models,
directly
show
biosafety
immunogenicity
DIMV,
investigate
its
tumour
vaccine
drug
carrier
in
cancer
treatment.
Extracellular
vesicles
(EVs)
are
nanosized,
membrane-bound
structures
that
have
emerged
as
promising
tools
for
drug
delivery,
especially
in
the
treatment
of
lysosomal
storage
disorders
(LSDs)
with
central
nervous
system
(CNS)
involvement.
This
review
highlights
unique
properties
EVs,
such
their
biocompatibility,
capacity
to
cross
blood-brain
barrier
(BBB),
and
potential
therapeutic
cargo
loading,
including
enzymes
genetic
material.
Current
therapies
LSDs,
like
enzyme
replacement
therapy
(ERT),
often
fail
address
neurological
symptoms
due
inability
BBB.
EVs
offer
a
viable
alternative,
allowing
targeted
delivery
CNS
improving
outcomes.
We
discuss
recent
advancements
engineering
modification
enhance
targeting,
circulation
time
stability,
provide
detailed
overview
application
Gaucher
Fabry
diseases,
Sanfilippo
syndrome.
Despite
potential,
challenges
remain
scaling
production,
ensuring
isolation
purity,
meeting
regulatory
requirements.
Future
developments
will
focus
on
overcoming
these
barriers,
paving
way
clinical
translation
EV-based
LSDs
other
disorders.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
ABSTRACT
This
study
presents
a
novel
method
and
device
for
the
hydrodynamic
production
of
extracellular
vesicles
(EVs)
derived
from
biomimetic
multicellular
3D
spheroids,
enabling
high-throughput
particle
release
that
is
10
to
20
times
higher
than
in
non-stimulated
conditions.
The
facilitates
formation
spheroids
human
mesenchymal
stem
cells
(hMSCs),
offering
an
all-in-one
approach
both
spheroid
generation
EV
release.
Production
are
reduced
just
few
hours,
with
yield
further
increased
by
alternating
periods
high
flow
recovery
sequential
approach.
Using
this
system,
we
explored
impact
starvation
conditions
on
protein
cargo
EVs,
identifying
distinct
markers
through
proteomics.
Specifically,
stimulation
enriched
EVs
plasma
membrane-derived
mitochondrial
proteins,
revealing
divergent
biogenesis
pathways.
Importantly,
produced
exhibited
therapeutic
properties,
demonstrated
effects
wound
healing,
angiogenesis,
anti-inflammatory
responses,
some
showing
enhanced
efficacy
under
stimulation.
Tumor-derived
exosomes
(TDEs)
mediate
oncogenic
communication,
which
modifies
target
cells
to
reinforce
a
tumor-promoting
microenvironment.
TDEs
support
cancer
progression
by
suppressing
anti-tumor
immune
responses,
promoting
metastasis,
and
conferring
drug
resistance.
Thus,
targeting
could
improve
the
efficacy
of
anti-cancer
treatments
control
metastasis.
Current
strategies
inhibit
TDE-mediated
communication
including
drug-based
genetic
modification-based
inhibition
TDE
release
and/or
uptake,
have
proved
be
inefficient.
In
this
work,
we
propose
surface
engineering
express
foreign
antigens
that
will
trigger
life-long
anti-TDE
responses.
The
possibility
combining
vaccines
with
other
such
as
chemotherapy,
radiotherapy,
targeted
therapy,
surgery
is
also
explored.
Extracellular
vesicles
(EVs)
are
generated
in
all
cells.
Systemic
administration
of
allogenic
EVs
derived
from
epithelial
and
mesenchymal
cells
has
been
shown
to
be
safe,
despite
carrying
an
array
functional
molecules,
including
thousands
proteins.
To
address
whether
cell-derived
can
modified
acquire
the
capacity
induce
immune
response,
we
engineered
293T
harbor
immunomodulatory
molecules
CD80,
OX40L,
PD-L1.
We
demonstrated
abundant
levels
these
proteins
EVs.
Functionally,
efficiently
elicited
positive
negative
costimulation
human
murine
T
In
setting
cancer
autoimmune
hepatitis,
modulated
cell
functions
altered
disease
progression.
OX40L
also
provided
enhanced
antitumor
activity
combination
with
anti-CTLA-4
melanoma-bearing
mice.
addition,
added
multiple
(EVmIM),
attempting
elicit
response
both
lymphoid
myeloid
compartments.
The
EVmIM
containing
4-1BBL,
CD40L,
CD2,
CD32
engaged
antigen
presenting
(APCs)
melanoma
tumors,
demonstrating
for
activity.
Our
work
provides
evidence
that
specific
responses
translational
potential
modulate
pathological
settings.
