Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis.
Nano Lett
; 20(2): 829-840, 2020 02 12.
Article
em En
| MEDLINE
| ID: mdl-31916446
ABSTRACT
Breast cancer metastases to bone poses a significant challenge for the administration of treatment strategies. The bone microenvironment, metastatic tumor cells, osteoclasts, and tumor-associated macrophages (TAMs) all play crucial and synergistic roles in creating a favorable environment for the proliferation, progression, and survival of the metastatic tumor, which in turn induces osteoclast-mediated bone destruction. In this study, we functionalized immunostimulatory cytosine-phosphate-guanosine (CpG)-loaded metal-organic framework (MOF) nanoparticles with bone targeting capabilities by surface modification with FDA approved antiresorptive bisphosphonate, zoledronic acid (ZOL). The functionalized bone targeting immunostimulatory MOF (BT-isMOF) nanoparticles demonstrates strong binding to calcium phosphate in vitro and exhibits specific targeting and accumulation in bone tissues in vivo. In vitro cellular and biochemical analyses demonstrated that the BT-isMOF nanoparticles could potently inhibit osteoclast formation and concomitantly induce macrophages polarization toward the M1 pro-inflammatory phenotype. Finally, using the intratibial murine model of breast cancer bone metastasis, we showed that the administration of BT-isMOF nanoparticles significantly suppressed osteoclast-mediated bone destruction and enhanced polarization of tumor-resident macrophages to M1 phenotype. Together, our data provides promising evidence for the potential therapeutic application of the BT-isMOF nanoparticles in the treatment of breast cancer bone metastases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Neoplasias da Mama
/
Nanopartículas
/
Estruturas Metalorgânicas
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2020
Tipo de documento:
Article