Bioengineered Nanospores Selectively Blocking LC3-Associated Phagocytosis in Tumor-Associated Macrophages Potentiate Antitumor Immunity.
ACS Nano
; 17(11): 10872-10887, 2023 06 13.
Article
en En
| MEDLINE
| ID: mdl-37192052
ABSTRACT
Although cytotoxic treatments hold tremendous potential in boosting antitumor immunity, efferocytosis of tumor-associated macrophages (TAMs) could negatively remove apoptotic tumor cells through LC3-associated phagocytosis (LAP), resulting in inefficient tumor antigen presentation and immunosuppressive tumor microenvironment. To address this issue, we developed TAM-targeting nanospores (PC-CW) inspired by the predominant tropism of Rhizopus oryzae toward macrophages. To construct PC-CW, we disguised poly(sodium-p-styrenesulfonate) (PSS)-coated polyethylenimine (PEI)-shRNA nanocomplexes with the cell wall of R. oryzae conidia. LAP blockade by PC-CW delayed the degradation of engulfed tumor debris within TAMs, which not only enhanced antigen presentation but also initiated the domino effect of the antitumor immune response through STING signaling and TAM repolarization. Benefiting from this, PC-CW successfully sensitized the immune microenvironment and amplified CD8+ T cell responses following chemo-photothermal therapy, leading to substantial tumor growth control and metastasis prevention in tumor-bearing mouse models. The bioengineered nanospores represent a simple and versatile immunomodulatory strategy targeting TAMs for robust antitumor immunotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Macrófagos Asociados a Tumores
/
Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
ACS Nano
Año:
2023
Tipo del documento:
Article