bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 22, 2024
Abstract
Systemic
delivery
of
immunotherapy
is
dose-limited
and
often
causes
serious
immune-related
adverse
events.
Intratumoral
injections
can
reduce
systemic
immunotoxicities
increase
concentrations
within
a
tumor.
However,
high
pressures
associated
with
direct
tumor
injection
limits
injectate
retention,
as
low
viscosity,
saline-based
solutions
rapidly
leak
out
tumors.
Viscoelastic
solids,
such
hydrogels,
improve
local
retention
co-formulated
immunotherapies
provide
sustained
delivery.
Prior
work
demonstrated
that
chitosan-based
hydrogel,
XCSgel,
was
shear-thinning,
self-healing,
injectable,
biocompatible,
clinically
imageable.
Here,
we
investigated
XCSgel
localized
intratumoral
platform
in
the
context
murine
models
orthotopic
triple-negative
breast
cancer.
The
immunotherapeutics
characterized
both
ex
vivo
via
fluorescence
imaging.
Histopathological
responses
to
alone
were
scored
by
veterinary
pathologist.
Initial
antitumor
studies
evaluated
range
cytokines
XCSgel.
Subsequent
rechallenge
efficacy
single
interleukin-12
(IL-12)
(XCSgel-IL12)
control
growth
primary
abscopal
tumors
while
inducing
protective
immunity.
Pharmacokinetics
quantified
dissemination
IL-12
consequent
production
interferon-gamma
following
co-formulation.
Spectral
flow
cytometry
used
document
changes
tumor-immune
microenvironment
(TIME).
resisted
leakage
slowly
released
three
model
cytokines.
could
be
tuned
for
faster
or
slower
release
embedded
therapeutics.
XCSgel-IL12
outperformed
formulations
other
commonly
A
eliminated
86%
E0771
20%
mWnt
TNBC
Mice
rendered
tumor-free
live
challenge.
also
67%
untreated
induced
profound
TIME,
including
3-fold
reduction
frequency
exhausted
CD8
+
T
cells
3.2-fold
activated,
proliferating
cells.
promising
well-suited
enhance
activity
potent
immunotherapeutics.
eliminate
solid
tumors,
indicating
may
not
required
Synopsis
novel
injectable
localize
triple
negative
cancer
injection.
Stem
cell
therapies
have
emerged
as
a
transformative
approach
in
modern
medicine,
with
the
potential
to
address
and
possibly
cure
broad
spectrum
of
diseases.
These
utilize
living
stem
cells
that
can
perform
complex
biological
functions
not
replicable
by
traditional
drugs.
an
expanding
therapeutic
landscape,
several
products
already
approved
numerous
clinical
trials
underway.
Among
various
types,
hematopoietic
(HSCs)
mesenchymal
(MSCs)
are
most
widely
studied.
In
this
review,
we
provide
detailed
analysis
current
landscape
therapies.
We
review
27
received
regulatory
approvals
discuss
800
ongoing
trials,
focus
on
HSCs
MSCs.
also
critical
challenges
be
addressed
facilitate
translation
Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
17(2), P. 205 - 205
Published: Feb. 6, 2025
Cancer
represents
a
significant
societal,
public
health,
and
economic
challenge.
Conventional
chemotherapy
is
based
on
systemic
administration;
however,
it
has
current
limitations,
including
poor
bioavailability,
high-dose
requirements,
adverse
side
effects,
low
therapeutic
indices,
the
development
of
multiple
drug
resistance.
These
factors
underscore
need
for
innovative
strategies
to
enhance
delivery
directly
tumours.
However,
local
treatment
also
presents
challenges,
penetration
through
endothelial
layers,
tissue
density
in
tumour
microenvironment,
interstitial
fluid
pressure,
physiological
conditions
within
tumour,
permanence
at
site
action.
Nanotechnology
promising
alternative
addressing
these
challenges.
This
narrative
review
elucidates
potential
nanostructured
formulations
cancer
treatment,
providing
illustrative
examples
an
analysis
advantages
challenges
associated
with
this
approach.
Among
nanoformulations
developed
breast,
bladder,
colorectal,
oral,
melanoma
cancer,
polymeric
nanoparticles,
liposomes,
lipid
nanohydrogels
have
demonstrated
particular
efficacy.
systems
permit
mucoadhesion
enhanced
penetration,
thereby
increasing
concentration
(bioavailability)
consequently
improving
anti-tumour
efficacy
potentially
reducing
effects.
In
addition
studies
indicating
chemotherapy,
nanocarriers
can
be
used
as
theranostic
approach
combination
irradiation
methods.
International Journal of Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 125612 - 125612
Published: April 1, 2025
The
immunosuppressive
tumor
immune
microenvironment
(TIME)
renders
glioblastoma
(GBM)
refractory
to
current
chemo-immunotherapeutics.
We
sought
explore
a
novel
approach
for
local
GBM-associated
TIME
immunomodulation
based
on
synergistic
combination
of
the
repurposed
chemotherapeutic
drugs
doxorubicin
(DOX),
which
acts
induce
immunogenic
cell
death
(ICD)
and
gemcitabine
(GEM),
depletes
myeloid-derived
suppressor
cells
(MDSCs).
conjugated
DOX
GEM
hyaluronic
acid
(HA)
improve
efficacy,
given
this
polymer's
ability
target
CD44
are
overexpressed
cancer
cells.
HA-DOX
HA-GEM
polymer-drug
conjugates
provided
cytotoxic
effects
maintained
ICD-related
properties
in
GBM
compared
free
drugs.
also
reverted
orthotopic
GL261
tumor-bearing
mice
by
selectively
depleting
MDSCs
reprogramming
M2-like
macrophages
towards
pro-inflammatory
M1-like
state,
resulting
controlled
growth.
Local
delivery
increased
median
survival
growth
an
SB28-GBM
mouse
model.
These
findings
highlight
potential
repurposing
clinically
applicable
chemotherapeutics
context
treatments
strategies
unresectable
GBM,
may
open
new
avenues
developing
innovative
therapies.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(19), P. 10539 - 10539
Published: Sept. 30, 2024
Cancer
therapy
is
constantly
evolving,
with
a
growing
emphasis
on
targeted
and
efficient
treatment
options.
In
this
context,
graphene
quantum
dots
(GQDs)
have
emerged
as
promising
agents
for
precise
drug
gene
delivery
due
to
their
unique
attributes,
such
high
surface
area,
photoluminescence,
up-conversion
biocompatibility.
GQDs
can
damage
cancer
cells
exhibit
intrinsic
photothermal
conversion
singlet
oxygen
generation
efficiency
under
specific
light
irradiation,
enhancing
effectiveness.
They
serve
direct
therapeutic
versatile
platforms
capable
of
being
easily
functionalized
various
targeting
molecules
agents.
However,
challenges
achieving
uniform
size
morphology,
bandgap
engineering,
scalability,
along
minimizing
cytotoxicity
the
environmental
impact
production,
must
be
addressed.
Additionally,
there
need
more
comprehensive
understanding
cellular
mechanisms
release
processes,
well
improved
purification
methods.
Integrating
into
existing
systems
enhances
efficacy
traditional
treatments,
offering
less
invasive
options
patients.
This
review
highlights
transformative
potential
in
while
acknowledging
that
researchers
overcome
broader
application.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
177, P. 117118 - 117118
Published: July 14, 2024
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
prevalent
malignant
tumors
in
contemporary
era,
representing
a
significant
global
health
concern.
Early
HCC
patients
have
mild
symptoms
or
are
asymptomatic,
which
promotes
onset
and
progression
disease.
Moreover,
advanced
insensitive
to
chemotherapy,
making
traditional
clinical
treatment
unable
block
cancer
development.
Sorafenib
(SFB)
first-line
targeted
drug
for
with
anti-angiogenesis
anti-tumor
cell
proliferation
effects.
However,
efficacy
SFB
constrained
by
its
off-target
distribution,
rapid
metabolism,
multi-drug
resistance.
In
recent
years,
nanoparticles
based
on
variety
materials
been
demonstrated
enhance
targeting
therapeutic
against
HCC.
Concurrently,
advent
joint
delivery
systems
has
furnished
crucial
empirical
evidence
reversing
This
review
will
summarize
application
nanotechnology
field
over
past
five
years.
It
focus
research
progress
combined
multiple
modalities
treatment.
International Journal of Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
664, P. 124623 - 124623
Published: Aug. 25, 2024
Docetaxel
(DTX)
is
a
recommended
treatment
in
patients
with
metastasic
prostate
cancer
(PCa),
despite
its
therapeutic
efficacy
limited
by
strong
systemic
toxicity.
However,
localized
PCa,
intratumoral
(IT)
administration
of
DTX
could
be
an
alternative
to
consider
that
may
help
overcome
the
disadvantages
conventional
intravenous
(IV)
therapy.
In
this
context,
we
here
present
first
vivo
preclinical
study
PCa
therapy
nanomedicines
mesoporous
silica
nanoparticles
(MSN)
and
IT
injection
over
xenograft
mouse
model
bearing
human
adenocarcinoma
tumors.
The
tolerability,
biodistribution
histopathology
after
have
been
investigated
for
nanomedicine
free
drug,
compared
IV
DTX.
obtained
results
demonstrate
allows
precise
selective
non-metastatic
minimize
diffusion
showing
superior
activity
than
route.
This
reducing
dose
one
order
widens
substantially
window
drug.
Furthermore,
use
as
promotes
antitumor
drug
accumulation
at
tumor
site,
improving
same
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 12, 2024
Abstract
Proteins
have
emerged
as
promising
therapeutics
in
oncology
due
to
their
great
specificity.
Many
treatment
strategies
are
developed
based
on
protein
biologics,
such
immunotherapy,
starvation
therapy,
and
pro‐apoptosis
while
some
biologics
entered
the
clinics.
However,
clinical
translation
is
severely
impeded
by
instability,
short
circulation
time,
poor
transmembrane
transportation,
immunogenicity.
Micro‐
nano‐particles‐based
drug
delivery
platforms
designed
solve
those
problems
enhance
therapeutic
efficacy.
This
review
first
summarizes
different
types
of
proteins
research
stages,
highlighting
administration
limitations.
Next,
various
micro‐
nano‐particles
described
demonstrate
how
they
can
overcome
The
potential
then
explored
efficacy
combinational
therapies.
Finally,
challenges
future
directions
carriers
discussed
for
optimized
delivery.
npj Systems Biology and Applications,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Nov. 20, 2024
Intratumoral
delivery
and
localized
chemotherapy
have
demonstrated
promise
in
tumor
treatment;
however,
the
rapid
drainage
of
therapeutic
agents
from
well-vascularized
tumors
limits
their
ability
to
achieve
maximum
efficacy.
Therefore,
innovative
approaches
are
needed
enhance
treatment
efficacy
such
tumors.
This
study
utilizes
a
mathematical
modeling
platform
assess
combination
therapy
using
anti-angiogenic
drugs
drug-loaded
nanoparticles.
Anti-angiogenic
included
reduce
blood
microvascular
density
facilitate
drug
retention
extracellular
space.
In
addition,
incorporating
negatively
charged
nanoparticles
aims
diffusion
distribution
within
The
findings
indicate
that,
case
direct
injection
free
drugs,
compounds
with
lower
rates
higher
coefficients
is
beneficial
for
achieving
broader
diffusion.
Otherwise,
tend
accumulate
primarily
around
site.
For
instance,
doxorubicin,
known
its
drainage,
requires
prior
an
high
rate
distribution,
enhancing
penetration
depth
by
200%.
Moreover,
results
demonstrate
that
effectively
disperse
throughout
tissue
due
coefficient.
faster
release
further
efficacy,
necessary
concentration
complete
eradication
compared
slower
rates.
demonstrates
potential
utilizing
loaded
exhibiting
through
intratumoral