In Situ Prodrug Activation by an Affibody-Ruthenium Catalyst Hybrid for HER2-Targeted Chemotherapy.
Angew Chem Int Ed Engl
; 61(26): e202202855, 2022 06 27.
Article
en En
| MEDLINE
| ID: mdl-35419921
ABSTRACT
Transition-metal catalysts exhibit great potential as therapeutic agents to inhibit tumor growth. However, the precise delivery and in situ catalysis are challenging in catalytic medicine. Herein, we report an anti-HER2 affibody-ruthenium catalyst hybrid, named Ru-HER2 for selective and effective killing of cancer cells. Ru-HER2 binds to the HER2 receptor on a tumor cell and in situ catalyzes the activation of gemcitabine prodrug, resulting in enhanced selectivity in suppression of tumor growth and reduction of side effects. Immunoblotting reveals that Ru-HER2 in combination with gemcitabine prodrug can not only induce DNA damage, but also effectively block the HER2 signaling pathway in cancer cells. Therefore, the HER2-targeted chemotherapy exhibits substantially high anticancer activity toward HER2-positive cancer cells in vitro and in vivo. In a word, we report the first affibody-ruthenium catalyst hybrid and reveal its potential for effective HER2-targeted cancer chemotherapy.
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Banco de datos:
MEDLINE
Asunto principal:
Rutenio
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Profármacos
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Neoplasias
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article