Arginine-assembly as NO nano-donor prevents the negative feedback of macrophage repolarization by mitochondrial dysfunction for cancer immunotherapy.
Biomaterials
; 306: 122474, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38271788
ABSTRACT
Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy. However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization. The strategy is to first apply reversible tagging of hydrophobic terephthalaldehyde to create an arginine nano-assembly, and then load a toll-like receptor 7/8 agonist resiquimod (R848) (R848@Arg). Through this strategy, a high loading efficiency of 40 % for the arginine and repolarization characteristics for TAMs can be achieved. Upon the macrophage repolarization by R848, NO can be intracellularly generated from the released arginine by the upregulated inducible nitric oxide synthase. Mechanistically, NO effectively prevented the negative feedback of the repolarized macrophage by mitochondrial dysfunction via blocking oxidative phosphorylation. Notably, R848@Arg significantly increased the tumor inhibition ratio by 3.13-fold as compared to the free R848 by maintaining the M1-like phenotype infiltrating into tumor. The Arg-assembly as NO nano-donor provides a promising method for effective repolarization of macrophages.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Mitocondriales
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Biomaterials
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos