Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis.

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.

• Authors: Yichuan Pang, Yao Fu, Chen Li, Zuoxing Wu, Weicheng Cao, Xi Hu, Xiaochen Sun, Wenxin He, Xiankun Cao, Daishun Ling, Qian Li, Chunhai Fan, Chi Yang, Xueqian Kong, An Qin
• Journal: Nano letters (Nano Lett) Vol. 20 Issue 2 Pg. 829-840 (02 12 2020) ISSN: 1530-6992 [Electronic] United States
• PMID: 31916446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Metal-Organic Frameworks
• Oligodeoxyribonucleotides
• cytosine-phosphorothioate guanine
• Zoledronic Acid

Topics

• Animals
• Bone Density Conservation Agents (chemistry, pharmacology)
• Bone Neoplasms (drug therapy, pathology, secondary)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Diphosphonates (chemistry, pharmacology)
• Female
• Humans
• Metal-Organic Frameworks (chemistry, pharmacology)
• Mice
• Nanoparticles (chemistry)
• Oligodeoxyribonucleotides (chemistry, pharmacology)
• Osteoclasts (drug effects)
• Osteolysis (drug therapy, pathology)
• Tumor-Associated Macrophages (drug effects)
• Zoledronic Acid (chemistry, pharmacology)