Targeting of Cisplatin-resistant Melanoma Using a Multivalent Ligand-presenting an Elastin-like Polypeptide
2020
Acquired
drug resistance is a common occurrence and the main cause
of melanoma treatment failure. Melanoma cells frequently developed
resistance against cisplatin during chemotherapy, and thus, targeting
delivery systems have been devised to decrease drug resistance, increase
therapeutic efficacy, and reduce side effects. We genetically engineered
a macromolecular carrier using the recursive directional ligation
method that specifically targets cisplatin-resistant (Cis-R) melanoma.
This carrier is composed of an elastin-like polypeptide (ELP) and
multiple copies of Cis-R melanoma-targeting ligands (M-peptide). The
designed M16E108 contains 16 targeting ligands
incorporated within an ELP and has an ideal thermal phase transition
at 39 °C. When treated to melanoma cells, M16E108 specifically accumulated in Cis-R B16F10 melanoma cells
and accumulated to a lesser extent in parental B16F10 cells. Consistently,
M16E108 exhibited efficient homing and longer
retention in tumor tissues in Cis-R melanoma-bearing mice than in
parental B16F10 melanoma-bearing mice. Thus, M16E108 was found to display considerable potential as a novel agent that
specifically targets cisplatin-resistant melanoma.
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