Enhanced Copper-Temozolomide Interactions by Protein for Chemotherapy against Glioblastoma Multiforme.
ACS Appl Mater Interfaces
; 11(45): 41935-41945, 2019 Nov 13.
Article
en En
| MEDLINE
| ID: mdl-31644262
ABSTRACT
Current treatment of recurrent glioblastoma multiforme (GBM) demands dose-intense temozolomide (TMZ), a prodrug of 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), based on the spontaneous hydrolysis of TMZ at basic pH. However, how to control the activity of MTIC remains unknown, which poses a particular challenge to search a reliable MTIC receptor. We reported that copper, for the first time, is found to recognize and bind MTIC in the process of TMZ degradation, which means copper can play an important role in enhancing the bioavailability of MTIC derived from TMZ. Using apoferritin as a model copper-bound protein, we studied the copper-TMZ interaction in protein and observed efficient MTIC immobilization with high binding efficiency (up to 92.9% based on original TMZ) and capacity (up to 185 MTIC moieties per protein). The system was stable against both alkaline and acidic pH and could be activated by glutathione to liberate MTIC, which paves a way to deliver a DNA-alkylating agent for both TMZ-sensitive and TMZ-resistant GBM chemotherapy. Our study provides a new insight for understanding the potential relationship between the special GBM microenvironment (specific copper accumulation) and the therapeutic effect of TMZ.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoferritinas
/
Neoplasias Encefálicas
/
Glioblastoma
/
Cobre
/
Temozolomida
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2019
Tipo del documento:
Article