Bioconjugate Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 12, 2025
Brain
tumors,
particularly
glioblastomas,
represent
the
most
complicated
cancers
to
treat
and
manage
due
their
highly
invasive
nature
protective
barriers
of
brain,
including
blood-brain
barrier
(BBB).
The
efficacy
currently
available
treatments,
viz.,
radiotherapy,
chemotherapy,
immunotherapy,
are
frequently
limited
by
major
side
effects,
drug
resistance,
restricted
penetration
into
brain.
Lipid
nanoparticles
(LNPs)
have
emerged
as
a
promising
targeted
delivery
system
for
brain
tumors.
nanocarriers
gained
tremendous
attention
tumor
therapeutics
multiple
encapsulation
abilities,
controlled
release,
better
biocompatibility,
ability
cross
BBB.
Herein,
detailed
analysis
design,
mechanisms,
therapeutic
benefits
LNPs
in
treatment
is
discussed.
Moreover,
we
also
discuss
safety
issues
clinical
developments
current
future
challenges.
Further,
focused
on
transformation
therapy
eliminating
effects
engineering
overcome
related
biological
barriers,
which
provide
personalized,
affordable,
low-risk
options.
International Journal of Pharmaceutics,
Journal Year:
2021,
Volume and Issue:
601, P. 120586 - 120586
Published: April 8, 2021
A
drawback
of
the
current
mRNA-lipid
nanoparticle
(LNP)
COVID-19
vaccines
is
that
they
have
to
be
stored
at
(ultra)low
temperatures.
Understanding
root
cause
instability
these
may
help
rationally
improve
mRNA-LNP
product
stability
and
thereby
ease
temperature
conditions
for
storage.
In
this
review
we
discuss
proposed
structures
mRNA-LNPs,
factors
impact
strategies
optimize
stability.
Analysis
reveals
mRNA,
ionizable
cationic
lipid
water
are
present
in
LNP
core.
The
neutral
helper
lipids
mainly
positioned
outer,
encapsulating,
wall.
mRNA
hydrolysis
determining
factor
instability.
It
currently
unclear
how
core
interacts
with
what
extent
degradation
prone
sites
protected
through
a
coat
lipids.
To
vaccines,
optimization
nucleotide
composition
should
prioritized.
Secondly,
better
understanding
milieu
exposed
LNPs
rationalize
adjustments
structure
preserve
integrity.
Moreover,
drying
techniques,
such
as
lyophilization,
promising
options
still
explored.
Proceedings of the National Academy of Sciences,
Journal Year:
2021,
Volume and Issue:
118(52)
Published: Dec. 21, 2021
Significance
Liver
accumulation
represents
a
significant
barrier
in
the
development
of
therapeutically
efficacious
nanoparticle
drug
delivery
systems.
Using
series
lipid
nanoparticles
with
distinct
organ-targeting
properties,
we
provide
evidence
for
plausible
mechanism
action
to
non-liver
tissues.
Following
intravenous
injection,
specific
proteins
blood
are
recruited
nanoparticle’s
surface
based
on
its
molecular
composition
and
they
endow
it
unique
biological
identity
that
governs
ultimate
fate
body.
An
innovative
paradigm
emerges
from
this
mechanistic
understanding
delivery—endogenous
targeting—wherein
is
rationally
engineered
interact
overcome
liver
target
organs.
Accounts of Chemical Research,
Journal Year:
2021,
Volume and Issue:
55(1), P. 2 - 12
Published: Dec. 1, 2021
ConspectusLipid
nanoparticles
(LNPs)
are
a
type
of
lipid
vesicles
that
possess
homogeneous
core.
These
widely
used
in
small-molecule
drug
and
nucleic
acid
delivery
recently
gained
much
attention
because
their
remarkable
success
as
platform
for
COVID-19
mRNA
vaccines.
Nonetheless,
the
utility
transient
protein
expression
induced
by
extends
far
beyond
vaccines
against
infectious
diseases─they
also
hold
promise
cancer
vaccines,
replacement
therapies,
gene
editing
components
rare
genetic
diseases.
However,
naked
is
inherently
unstable
prone
to
rapid
degradation
nucleases
self-hydrolysis.
Encapsulation
within
LNPs
protects
from
extracellular
ribonucleases
assists
with
intracellular
delivery.In
this
Account,
we
discuss
core
features
RNA
delivery.
We
focus
our
on
designed
deliver
mRNA;
however,
include
examples
siRNA-LNP
where
appropriate
highlight
commonalities
dissimilarities
due
structure.
First,
introduce
concept
LNPs,
advantages
disadvantages
utilizing
acids
therapeutic
agents,
general
reasoning
behind
molecular
makeup
LNPs.
briefly
most
recent
clinical
successes
LNP-based
therapies.
Second,
describe
theory
methods
LNP
self-assembly.
The
common
idea
all
preparation
inducing
electrostatic
interactions
between
charged
lipids
promoting
nanoparticle
growth
via
hydrophobic
interactions.
Third,
break
down
composition
special
fundamental
properties
purposes
each
component.
This
includes
identified
design
criteria,
commercial
sourcing,
impact
trafficking,
contribution
One
key
ionizable
lipids,
which
initiate
binding
endosomal
membranes
facilitate
cytosolic
release;
roles
other
should
not
be
disregarded,
they
associated
stability,
clearance,
distribution
Fourth,
review
attributes
constructs
whole
can
heavily
influence
size,
charge,
internal
structure,
packing,
membrane
hydration,
affinity
toward
biomacromolecules.
specific
techniques
examine
these
how
adjusted.
Finally,
offer
perspective
future
therapies
some
questions
remain
realm
formulation
optimization.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Sept. 23, 2022
Abstract
Lipid
nanoparticles
(LNPs)
are
effective
vehicles
to
deliver
mRNA
vaccines
and
therapeutics.
It
has
been
challenging
assess
packaging
characteristics
in
LNPs,
including
payload
distribution
capacity,
which
critical
understanding
structure-property-function
relationships
for
further
carrier
development.
Here,
we
report
a
method
based
on
the
multi-laser
cylindrical
illumination
confocal
spectroscopy
(CICS)
technique
examine
lipid
contents
LNP
formulations
at
single-nanoparticle
level.
By
differentiating
unencapsulated
mRNAs,
empty
LNPs
mRNA-loaded
via
coincidence
analysis
of
fluorescent
tags
different
components,
quantitatively
resolving
single-mRNA
fluorescence,
reveal
that
commonly
referenced
benchmark
formulation
using
DLin-MC3
as
ionizable
contains
mostly
2
mRNAs
per
loaded
with
presence
40%–80%
depending
assembly
conditions.
Systematic
control
variables
reveals
kinetically
controlled
mechanism
governs
capacity
LNPs.
These
results
form
foundation
holistic
molecular
