A tumor-targeted Ganetespib-zinc phthalocyanine conjugate for synergistic chemo-photodynamic therapy.
Eur J Med Chem
; 151: 294-303, 2018 May 10.
Article
en En
| MEDLINE
| ID: mdl-29627724
ABSTRACT
Therapeutic effects of photodynamic therapy (PDT) are limited by the selectivity of photosensitizer (PS). Herein, a novel tumor-targeted drug-PS conjugate (Gan-ZnPc) which integrated with zinc phthalocyanine (ZnPc) and Ganetespib has been developed. ZnPc is a promising PS with remarkable photosensitization ability. Ganetespib is a heat shock protein 90 (Hsp90) inhibitor with preferential tumor selectivity and conjugated to ZnPc as a tumor-targeted ligand. The multifunctional small molecule conjugate, Gan-ZnPc, could be bound to extracellular Hsp90 and then selectively internalized into the tumor cells, followed by the generation of abundant intracellular reactive oxygen species (ROS) upon irradiation. Besides, Gan-ZnPc can arrest cell proliferation and induce apoptosis by the inhibition of Hsp90. Herein, with combination of the inhibition of Hsp90 and the generation of cytotoxic ROS, Gan-ZnPc implements tumor selectivity, concentrated PDT and chemotherapy in a synergistic manner, which results in highly effective anti-tumor activity in vitro and in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Triazoles
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Fármacos Fotosensibilizantes
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Indoles
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Neoplasias Mamarias Experimentales
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2018
Tipo del documento:
Article
Pais de publicación:
FR
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FRANCE
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FRANCIA
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FRANÇA