Repolarizing Tumor-Associated Macrophages and inducing immunogenic cell Death: A targeted liposomal strategy to boost cancer immunotherapy.
Int J Pharm
; 651: 123729, 2024 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-38142016
ABSTRACT
Cancer immunotherapy has shown promise in treating various malignancies. However, the presence of an immunosuppressive tumor microenvironment (TME) triggered by M2 tumor-associated macrophages (TAMs) and the limited tumor cell antigenicity have hindered its broader application. To address these challenges, we developed DOX/R837@ManL, a liposome loaded with imiquimod (R837) and doxorubicin (DOX), modified with mannose-polyethylene glycol (Man-PEG). DOX/R837@ManL employed a mannose receptor (MRC1)-mediated targeting strategy, allowing it to accumulate selectively at M2 Tumor associated macrophages (TAMs) and tumor sites. R837, an immune adjuvant, promoted the conversion of immunosuppressive M2 TAMs into immunostimulatory M1 TAMs, and reshaped the immunosuppressive TME. Simultaneously, DOX release induced immunogenic cell death (ICD) in tumor cells and enhanced tumor cell antigenicity by promoting dendritic cells (DCs) maturation. Through targeted delivery, the synergistic action of R837 and DOX activated innate immunity and coordinated adaptive immunity, enhancing immunotherapy efficacy. In vivo experiments have demonstrated that DOX/R837@ManL effectively eliminated primary tumors and lung metastases, while also preventing tumor recurrence post-surgery. These findings highlighted the potential of DOX/R837@ManL as a promising strategy for cancer immunotherapy.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Lipossomos
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China