Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH-Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy.
Nano Lett
; 17(6): 3822-3829, 2017 06 14.
Article
en En
| MEDLINE
| ID: mdl-28488871
ABSTRACT
Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ-945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in multiple tumor models. The underlying mechanism studies suggest that the designer pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but also modulates the tumor immune environment to eventually augment the antitumor effect of CD8+ cytotoxic T cells through TAMs depletion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Portadores de Fármacos
/
Nanopartículas
/
Macrófagos
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nano Lett
Año:
2017
Tipo del documento:
Article
País de afiliación:
China