Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(4), P. 2294 - 2304
Published: Jan. 18, 2023
Lipid
nanoparticles
(LNPs)
are
the
most
clinically
advanced
delivery
vehicles
for
RNA
and
have
enabled
development
of
RNA-based
drugs
such
as
mRNA
COVID-19
vaccines.
Functional
by
an
LNP
greatly
depends
on
inclusion
ionizable
lipid,
small
changes
to
these
lipid
structures
can
significantly
improve
delivery.
However,
structure–function
relationships
between
lipids
poorly
understood,
especially
LNPs
administered
intramuscularly.
Here,
we
show
that
iterative
design
a
novel
series
generates
key
structure–activity
enables
optimization
chemically
distinct
with
efficacy
is
on-par
current
state
art.
We
find
combination
comprising
ethanolamine
core
apparent
pKa
6.6
6.9
maximizes
intramuscular
Furthermore,
report
nonlinear
relationship
lipid-to-mRNA
mass
ratio
protein
expression,
suggesting
critical
exists
may
depend
structure.
Our
findings
add
mechanistic
understanding
demonstrate
hydrogen
bonding,
ionization
behavior,
parameters
affecting
validate
insights
applying
them
rational
new
lipids.
Overall,
our
strategy
efficiently
potent
This
hypothesis-driven
method
reveals
lay
foundation
in
future
LNP-RNA
drugs.
foresee
this
be
extended
other
beyond
expression.
Cell,
Journal Year:
2022,
Volume and Issue:
185(15), P. 2806 - 2827
Published: July 1, 2022
In
vivo
gene
editing
therapies
offer
the
potential
to
treat
root
causes
of
many
genetic
diseases.
Realizing
promise
therapeutic
in
requires
ability
safely
and
efficiently
deliver
agents
relevant
organs
tissues
vivo.
Here,
we
review
current
delivery
technologies
that
have
been
used
enable
editing,
including
viral
vectors,
lipid
nanoparticles,
virus-like
particles.
Since
no
single
modality
is
likely
be
appropriate
for
every
possible
application,
compare
benefits
drawbacks
each
method
highlight
opportunities
future
improvements.
MedComm,
Journal Year:
2023,
Volume and Issue:
4(4)
Published: July 14, 2023
Nanoparticles
(NPs)
have
become
one
of
the
most
popular
objects
scientific
study
during
past
decades.
However,
despite
wealth
reports,
still
there
is
a
gap,
particularly
in
health
toxicology
studies,
underlying
mechanisms,
and
related
evaluation
models
to
deeply
understanding
NPs
risk
effects.
In
this
review,
we
first
present
comprehensive
landscape
applications
on
health,
especially
addressing
role
medical
diagnosis,
therapy.
Then,
toxicity
systems
introduced.
We
describe
detail
effects
various
systems,
including
respiratory,
nervous,
endocrine,
immune,
reproductive
carcinogenicity
NPs.
Furthermore,
unravels
mechanisms
ROS
accumulation,
mitochondrial
damage,
inflammatory
reaction,
apoptosis,
DNA
cell
cycle,
epigenetic
regulation.
addition,
classical
such
as
lines
mice
emerging
3D
organoids
used
for
evaluating
or
are
both
Overall,
review
presents
critical
summary
state
NPs,
giving
readers
more
better
remedy
key
gaps
knowledge
techniques.
ACS Nano,
Journal Year:
2022,
Volume and Issue:
16(8), P. 11769 - 11780
Published: June 27, 2022
Humans
commonly
have
low
level
antibodies
to
poly(ethylene)
glycol
(PEG)
due
environmental
exposure.
Lipid
nanoparticle
(LNP)
mRNA
vaccines
for
SARS-CoV-2
contain
small
amounts
of
PEG,
but
it
is
not
known
whether
PEG
are
enhanced
by
vaccination
and
what
their
impact
on
particle–immune
cell
interactions
in
human
blood.
We
studied
plasma
from
130
adults
receiving
either
the
BNT162b2
(Pfizer-BioNTech)
or
mRNA-1273
(Moderna)
no
vaccine
PEG-specific
antibodies.
Anti-PEG
IgG
was
detected
prior
significantly
boosted
a
mean
13.1-fold
(range
1.0–70.9)
following
1.78-fold
0.68–16.6)
vaccination.
IgM
increased
68.5-fold
0.9–377.1)
2.64-fold
(0.76–12.84)
vaccination,
respectively.
The
rise
associated
with
significant
increase
association
clinically
relevant
PEGylated
LNPs
blood
phagocytes
ex
vivo.
did
specific
neutralizing
antibody
response
However,
elevated
levels
vaccine-induced
anti-PEG
correlated
systemic
reactogenicity
two
doses
conclude
that
can
be
LNP
an
particle–leukocyte
longer-term
clinical
induced
lipid
should
monitored.
It
may
useful
identify
suitable
alternatives
developing
next-generation
overcome
immunogenicity
future.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(21), P. 9184 - 9205
Published: May 10, 2022
An
inconvenient
hurdle
in
the
practice
of
nanomedicine
is
protein
corona,
a
spontaneous
collection
biomolecular
species
by
nanoparticles
living
systems.
The
corona
dynamic
composition
and
may
entail
improved
water
suspendability
compromised
delivery
targeting
to
nanoparticles.
How
much
this
nonspecific
ensemble
determined
chemistry
nanoparticle
core
its
surface
functionalization,
how
entity
dictated
biological
environments
that
vary
spatiotemporally
vivo?
do
we
"live
with"
exploit
without
significantly
sacrificing
efficacy
nanomedicines
diagnosing
curing
human
diseases?
This
article
discusses
chemical
biophysical
signatures
ponders
challenges
ahead
for
field
nanomedicine.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(51)
Published: May 17, 2023
Abstract
Messenger
RNA
(mRNA)
has
received
great
attention
in
the
prevention
and
treatment
of
various
diseases
due
to
success
coronavirus
disease
2019
(COVID‐19)
mRNA
vaccines
(Comirnaty
Spikevax).
To
meet
therapeutic
purpose,
it
is
required
that
must
enter
target
cells
express
sufficient
proteins.
Therefore,
development
effective
delivery
systems
necessary
crucial.
Lipid
nanoparticle
(LNP)
represents
a
remarkable
vehicle
indeed
accelerated
applications
humans,
as
several
mRNA‐based
therapies
have
already
been
approved
or
are
clinical
trials.
In
this
review,
focus
on
mRNA‐LNP‐mediated
anticancer
therapy.
It
summarizes
main
strategies
mRNA‐LNP
formulations,
discusses
representative
approaches
cancer,
points
out
current
challenges
possible
future
directions
research
field.
hoped
these
delivered
messages
can
help
further
improve
application
technology
cancer
