Site-Selective Zwitterionic Poly(caprolactone-carboxybetaine)-Growth Hormone Receptor Antagonist Conjugate: Synthesis and Biological Evaluation
Jane K. Yang,
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Madeline B. Gelb,
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Kyle Tamshen
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et al.
Biomacromolecules,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 29, 2024
Zwitterionic
polymers
have
been
found
to
be
biocompatible
alternatives
poly(ethylene
glycol)
(PEG)
for
conjugation
proteins.
This
work
reports
the
site-selective
of
poly(caprolactone-carboxybetaine)
(pCLZ)
human
growth
hormone
receptor
antagonist
(GHA)
B2036-alkyne
and
investigation
safety,
activity,
pharmacokinetics.
Azide-end-functionalized
pCLZs
were
synthesized
conjugated
GHA
via
copper-catalyzed
click
reaction.
The
resulting
inhibitory
bioactivity
concentration
responses
in
Ba/F3-GHR
cells
compared
those
PEGylated
B2036.
IgG
IgM
antibody
production
was
tested
mice,
no
measurable
or
cytokine
detected
pCLZ
conjugate.
Using
Language: Английский
Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes
Cancers,
Journal Year:
2024,
Volume and Issue:
16(15), P. 2636 - 2636
Published: July 24, 2024
Drug
resistance
in
melanoma
is
a
major
hindrance
cancer
therapy.
Growth
hormone
(GH)
plays
pivotal
role
contributing
to
the
chemotherapy.
Knocking
down
or
blocking
GH
receptor
has
been
shown
sensitize
tumor
cells
Extensive
studies
have
demonstrated
that
exosomes,
subset
of
extracellular
vesicles,
play
an
important
drug
by
transferring
key
factors
In
this
study,
we
explore
how
modulates
exosomal
cargoes
from
and
their
resistance.
We
treated
with
GH,
doxorubicin,
GHR
antagonist,
pegvisomant,
analyzed
exosomes
released.
Additionally,
administered
these
recipient
cells.
The
GH-treated
released
elevated
levels
ABC
transporters
(ABCC1
ABCB1),
N-cadherin,
MMP2,
enhancing
migration
antagonism
reduced
levels,
restoring
sensitivity
attenuating
migration.
Overall,
our
findings
highlight
novel
modulating
drive
chemoresistance
metastasis
melanoma.
This
understanding
provides
insights
into
mechanisms
suggests
as
potential
therapy
overcome
treatment.
Language: Английский