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Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis.
- Source :
-
Nano letters [Nano Lett] 2020 Feb 12; Vol. 20 (2), pp. 829-840. Date of Electronic Publication: 2020 Jan 14. - Publication Year :
- 2020
-
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.
- Subjects :
- Animals
Bone Density Conservation Agents chemistry
Bone Density Conservation Agents pharmacology
Bone Neoplasms pathology
Bone Neoplasms secondary
Breast Neoplasms pathology
Cell Line, Tumor
Diphosphonates chemistry
Diphosphonates pharmacology
Female
Humans
Metal-Organic Frameworks chemistry
Mice
Oligodeoxyribonucleotides chemistry
Oligodeoxyribonucleotides pharmacology
Osteoclasts drug effects
Osteolysis drug therapy
Osteolysis pathology
Tumor-Associated Macrophages drug effects
Zoledronic Acid chemistry
Zoledronic Acid pharmacology
Bone Neoplasms drug therapy
Breast Neoplasms drug therapy
Metal-Organic Frameworks pharmacology
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6992
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nano letters
- Publication Type :
- Academic Journal
- Accession number :
- 31916446
- Full Text :
- https://doi.org/10.1021/acs.nanolett.9b02916