Nano Research,
Journal Year:
2024,
Volume and Issue:
17(10), P. 9095 - 9102
Published: June 27, 2024
Abstract
Activated
fibroblasts
are
major
mediators
of
pulmonary
fibrosis.
Fibroblasts
generally
found
in
the
connective
tissue
but
upon
activation
can
generate
excess
extracellular
matrix
(ECM)
lung
interstitial
section.
Therefore,
one
most
targeted
cells
for
treating
idiopathic
fibrosis
(IPF).
Here,
we
develop
an
anti-fibrotic
platform
that
modulate
both
lysophosphatidic
acid
receptor
1
(LPA
)
and
inflammatory
pathway
through
tumor
necrosis
factor
α
-induced
protein
3
(TNFAIP3,
also
known
as
A20)
fibroblasts.
First,
synthesized
a
series
LPA
antagonists,
AM095
AM966,
derived
amino
lipids
(LA
lipids)
which
were
formulated
into
LA-lipid
nanoparticles
(LA-LNPs)
encapsulating
mRNA.
Specifically,
LA5-LNPs,
with
AM966
head
group
biodegradable
acetal
lipid
tails,
showed
efficient
A20
mRNA
delivery
to
vitro
(80.2%
±
1.5%)
ex
vivo
(17.2%
0.4%).
When
treated
primary
mouse
(MLF),
this
formulation
inhibited
fibroblast
migration
collagen
production,
thereby
slowing
progression
IPF.
Overall,
LA5-LNPs
encapsulated
is
novel
offering
potential
approach
regulate
treatment
Dentistry Journal,
Journal Year:
2025,
Volume and Issue:
13(2), P. 79 - 79
Published: Feb. 13, 2025
Background:
Recent
advances
in
mRNA
vaccine
technology,
accelerated
by
the
global
COVID-19
pandemic,
have
generated
significant
interest
their
applications
beyond
infectious
diseases.
Dentistry
has
emerged
as
a
promising
field
for
exploring
potential
of
mRNA-based
therapies
preventing
and
treating
oral
Objectives:
This
narrative
review
aims
to
evaluate
current
status
development
its
preclinical
health,
focusing
on
periodontal
disease,
dental
caries,
regenerative
medicine,
implantology,
cancer.
Methods:
The
synthesizes
findings
from
studies,
including
research
conducted
animal
models
vitro,
assess
modulate
immune
responses
promote
tissue
regeneration
cavity.
Clinical
trials
were
only
mentioned
context
broader
areas
implementation
such
oncology
immunotherapy.
Results:
studies
highlight
capacity
vaccines
enhance
body's
response
facilitate
repair
processes.
Despite
these
results,
challenges
persist
delivering
effectively
within
complex
environment.
These
include
stability,
delivery
mechanisms,
modulation
responses.
Conclusions:
While
offer
promise
revolutionizing
health
care,
they
face
notable
limitations
concerning
safety,
efficacy,
clinical
feasibility.
Overcoming
obstacles
through
further
is
essential
unlock
full
translational
ensure
safe
effective
integration
into
practice.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 30, 2025
Abstract
Intranasal
delivery
of
mRNA
vaccines
offers
promising
opportunities
to
combat
airborne
viruses
like
SARS‐CoV‐2
by
provoking
mucosal
immunity,
which
not
only
defends
against
respiratory
infection
but
also
prevents
contagious
transmission.
However,
the
development
nasal
has
been
hampered
lack
effective
means
overcome
mucus
barrier.
Herein,
ionizable
lipid‐incorporated
liquid
lipid
nanoparticles
(iLLNs)
capable
delivering
cargo
across
airway
mucosa
are
designed.
Adjusting
ratios
and
cationic
lipids
allows
fine‐tuning
p
K
a
iLLNs
range
pH
(5.5–6.5),
thus
facilitating
penetration
via
formation
near‐neutral,
PEGylated
muco‐inert
surfaces.
When
nasally
administered
mice,
top
candidate
iLLN‐2/mRNA
complexes
enable
about
60‐fold
greater
reporter
gene
expression
in
cavity,
compared
benchmark
mRNA‐lipid
(ALC‐LNP)
having
same
composition
as
that
BNT162b2
vaccine.
Moreover,
prime‐boost
intranasal
immunization
elicits
magnitude
spike‐specific
IgA
IgG
response
than
ALC‐LNP,
without
triggering
any
noticeable
inflammatory
reactions.
Taken
together,
these
results
provide
useful
insights
for
design
deliverable
formulations
prophylactic
applications.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 10, 2025
Over
the
past
decades,
significant
progress
has
been
made
in
understanding
of
non-small
cell
lung
cancer
(NSCLC)
biology
and
tumor
progression
mechanisms,
resulting
development
novel
strategies
for
early
detection
wide-ranging
care
approaches.
Since
their
introduction,
over
20
years
ago,
targeted
therapies
with
tyrosine
kinase
inhibitors
(TKIs)
have
revolutionized
treatment
landscape
NSCLC.
Nowadays,
remain
gold
standard
many
patients,
but
still
they
suffer
from
adverse
effects,
including
unexpected
toxicity
intrinsic
acquired
resistance
mutations,
which
lead
to
relapse.
The
adoption
immune
checkpoint
(ICIs)
2015,
offered
exceptional
survival
benefits
patients
without
targetable
alterations.
Despite
this
notable
progress,
challenges
remain,
as
not
all
respond
favorably
ICIs,
therapy
can
develop
time.
A
crucial
factor
influencing
clinical
response
immunotherapy
is
microenvironment
(TME).
TME
pivotal
orchestrating
interactions
between
neoplastic
cells
system,
growth
outcomes.
In
review,
we
discuss
how
intricate
relationship
success
survey
current
state
intervention,
a
focus
on
forthcoming
promising
chimeric
antigen
receptor
(CAR)
T
sets
major
obstacles
CAR-T
therapies,
creating
conditions
that
suppress
response,
inducing
exhaustion.
To
enhance
efficacy,
specific
efforts
associated
NSCLC,
should
definitely
TME-related
immunosuppression
escape
by
combining
blockades.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 13, 2025
Introduction
Mycobacterium
tuberculosis
(
Mtb
)
is
the
causative
agent
of
(TB),
a
disease
with
severe
global
burden.
The
intractability
has
prevented
identification
clear
correlates
protection
against
TB
and
hindered
development
novel
vaccines
that
are
urgently
required.
Lipid
nanoparticle
(LNP)-formulated
mRNA
highly
promising
vaccine
platform
yet
to
be
thoroughly
applied
TB.
Methods
We
selected
five
antigens
(PPE15,
ESAT6,
EspC,
EsxI,
MetE)
evaluated
their
potential
as
LNP-formulated
vaccines,
both
when
each
antigen
was
delivered
individually,
all
were
combined
in
mix
regimen
(m-Mix).
Results
Each
construct
demonstrated
unique
cellular
humoral
immunogenicity,
m-Mix,
well
single
conferred
significant
murine
challenge
model.
Whilst
potent
immune
responses
maintained
boost
BCG,
there
no
additional
increase
efficacy
BCG.
Combination
m-Mix
recombinant,
replication-deficient
chimpanzee
adenovirus
(ChAdOx1),
heterologous
prime-boost
delivery
(C-m-Mix),
appeared
result
increased
upon
infection,
than
either
alone.
Discussion
This
work
warrants
further
investigation
for
TB,
whilst
indicating
C-m-Mix
progress
stages
development.
