Circulating immunotherapy strategy based on pyroptosis and STING pathway: Mn-loaded paclitaxel prodrug nanoplatform against tumor progression and metastasis.
Biomaterials
; 306: 122472, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38280315
ABSTRACT
Immunotherapy has emerged as a promising strategy against tumors. However, its efficacy is limited by low immunogenicity, poor antigen presentation, and inadequate lymphocyte infiltration. Herein, we develop a nanoplatform (Mn-HSP) loaded with manganese ions (Mn2+) and paclitaxel (PTX) prodrug based on hyaluronic acid. PTX in Mn-HSP induces DNA damage and pyroptosis to release tumor-associated antigens (TAAs), enhancing tumor-specific adaptive immunity. Meanwhile, Mn2+ in Mn-HSP, together with PTX-induced DNA damage, activates the stimulator of interferon gene (STING) pathway to amplify innate immunity. Mn-HSP combines with adaptive and innate immunity, effectively enhancing the presentation of antigen-presenting cells (APCs) and promoting tumor infiltration of cytotoxic T lymphocytes (CTLs). In turn, the granzyme B (GZMB) secreted by CTLs triggers pyroptosis again, thereby establishing a "circulating immunotherapy" against tumors. Our results demonstrate that Mn-HSP efficiently inhibits primary breast tumors, as well as rechallenge tumors and lung metastasis in vivo. Therefore, the circulating immunotherapy that combines pyroptosis mediated adaptive immunity and STING pathway amplified innate immunity provides a novel strategy for enhancing tumor immunotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pulmonares
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Biomaterials
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos