Multiple Functions Integrated inside a Single Molecule for Amplification of Photodynamic Therapy Activity.
Mol Pharm
; 17(1): 190-201, 2020 01 06.
Article
en En
| MEDLINE
| ID: mdl-31804837
ABSTRACT
Nitric oxide (NO) can play both prosurvival and prodeath roles in photodynamic therapy (PDT). The generation efficiency of peroxynitrite anions (ONOO-), by NO and superoxide anions (O2â¢-), significantly influenced the outcome. Reports indicated that such efficiency is closely related to the distance between NO and O2â¢-. Thus, in this manuscript, l-arginine (Arg) ethyl ester-modified zinc phthalocyanine (Arg-ZnPc) was designed and synthesized as a photosensitizer (PS) and NO donor. Post light irradiation, the guanido of Arg-ZnPc can be effectively oxidized by the generated reactive oxygen species (ROS) in the PDT process to release NO. Such a strategy could ensure O2â¢- and NO generation in the same place at the same time to guarantee effective ONOO- formation. In addition, NO has other multiple synergistic cancer treatment functions, including tumor tissue vasodilatation for drug extravasation promotion, P-glycoprotein (P-gp) downregulation for drug efflux inhibition, and glutathione depletion for cancer cell endogenous antioxidant defense destruction. In vitro and in vivo results indicated that the effective ONOO- formation and multiple functions of Arg-ZnPc could synergistically enhance its PDT activity and ensure satisfactory cancer treatment outcome.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Fotoquimioterapia
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Fármacos Fotosensibilizantes
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Superóxidos
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Indoles
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Neoplasias
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Óxido Nítrico
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China