Current progress and remaining challenges of peptide–drug conjugates (PDCs): next generation of antibody-drug conjugates (ADCs)?
Journal of Nanobiotechnology,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: April 22, 2025
Drug
conjugates
have
emerged
as
a
promising
alternative
delivery
system
designed
to
deliver
an
ultra-toxic
payload
directly
the
target
cancer
cells,
maximizing
therapeutic
efficacy
while
minimizing
toxicity.
Among
these,
antibody-drug
(ADCs)
garnered
significant
attention
from
both
academia
and
industry
due
their
great
potential
for
therapy.
However,
peptide-drug
(PDCs)
offer
several
advantages
over
ADCs,
including
more
accessible
industrial
synthesis,
versatile
functionalization,
high
tissue
penetration,
rapid
clearance
with
low
immunotoxicity.
These
factors
position
PDCs
up-and-coming
drug
candidates
future
Despite
potential,
face
challenges
such
poor
pharmacokinetic
properties
bioactivity,
which
hinder
clinical
development.
How
design
meet
needs
is
big
challenge
urgent
resolve.
In
this
review,
we
first
carefully
analyzed
general
consideration
of
successful
PDC
learning
ADCs.
Then,
summarised
basic
functions
each
component
construct,
comprising
peptides,
linkers
payloads.
The
peptides
in
were
categorized
into
three
types:
tumor
targeting
cell
penetrating
peptide
self-assembling
peptide.
We
then
these
delivery,
overcoming
resistance,
controlling
release
improving
reduced
non-specific
To
better
understand
druggability
PDCs,
discussed
pharmacokinetics
also
briefly
introduced
current
trials.
Lastly,
perspectives
development
oncology
PDC.
This
review
aimed
provide
useful
information
construction
applications.
Language: Английский
Recent Advances in Augmenting the Therapeutic Efficacy of Peptide–Drug Conjugates
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 23, 2025
There
is
an
urgent
need
for
the
development
of
safe
and
effective
modalities
treatment
diseases
owing
to
drug
resistance,
undesired
side
effects,
poor
clinical
outcomes.
Combining
cell-targeting
efficient
cell-killing
properties,
peptide-drug
conjugates
(PDCs)
have
demonstrated
superior
efficacy
compared
with
peptides
payloads
alone.
However,
innovative
molecular
designs
PDCs
are
essential
further
improving
targeting
precision,
protease
resistance
stability,
cell
permeability,
overall
efficacy.
Several
strategies
been
developed
address
these
challenges,
such
as
multivalency
approaches,
bispecific
targeting,
long-acting
PDCs.
Other
novel
strategies,
including
overcoming
biological
barriers,
conjugating
functional
payloads,
macropinocytosis,
also
shown
promise.
This
perspective
compiles
most
recent
enhancing
PDC
efficacy,
highlights
key
advancements
in
PDC,
provides
insights
on
future
directions
Language: Английский