Targeting folate receptor ß positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex.
Signal Transduct Target Ther
; 5(1): 6, 2020 01 22.
Article
em En
| MEDLINE
| ID: mdl-32296026
ABSTRACT
Tumor-associated macrophages (TAMs) facilitate cancer progression by promoting tumor invasion, angiogenesis, metastasis, inflammatory responses, and immunosuppression. Folate receptor ß (FRß) is overexpressed in TAMs. However, the clinical significance of FRß-positive macrophages in lung cancer remains poorly understood. In this study, we verified that FRß overexpression in lung cancer TAMs was associated with poor prognosis. We utilized a folate-modified lipoplex comprising a folate-modified liposome (F-PLP) delivering a BIM-S plasmid to target both lung cancer cells and FRß-positive macrophages in the tumor microenvironment. Transfection of LL/2 cells and MH-S cells with F-PLP/pBIM induced cell apoptosis. Injection of F-PLP/pBIM into LL/2 and A549 lung cancer models significantly depleted FRß-positive macrophages and reduced tumor growth. Treatment of tumor-bearing mice with F-PLP/pBIM significantly inhibited tumor growth in vivo by inducing tumor cell and macrophage apoptosis, reducing tumor proliferation, and inhibiting tumor angiogenesis. In addition, a preliminary safety evaluation demonstrated a good safety profile of F-PLP/pBIM as a gene therapy administered intravenously. This work describes a novel application of lipoplexes in lung cancer targeted therapy that influences the tumor microenvironment by targeting TAMs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor 2 de Folato
/
Ácido Fólico
/
Macrófagos Associados a Tumor
/
Neoplasias Pulmonares
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article