Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy.
J Control Release
; 368: 84-96, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38331004
ABSTRACT
Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc-) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ferroptose
/
Glioma
Limite:
Animals
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China