PMID- 31916446 OWN - NLM STAT- MEDLINE DCOM- 20210104 LR - 20210104 IS - 1530-6992 (Electronic) IS - 1530-6984 (Linking) VI - 20 IP - 2 DP - 2020 Feb 12 TI - Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis. PG - 829-840 LID - 10.1021/acs.nanolett.9b02916 [doi] AB - 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. FAU - Pang, Yichuan AU - Pang Y AD - Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , People's Republic of China. FAU - Fu, Yao AU - Fu Y AD - Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry , Zhejiang University , Hangzhou 310027 , People's Republic of China. FAU - Li, Chen AU - Li C AD - Guangxi Key Laboratory of Regenerative Medicine , Guangxi Medical University , Guangxi 530021 , People's Republic of China. FAU - Wu, Zuoxing AU - Wu Z AD - Guangxi Key Laboratory of Regenerative Medicine , Guangxi Medical University , Guangxi 530021 , People's Republic of China. FAU - Cao, Weicheng AU - Cao W AD - Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry , Zhejiang University , Hangzhou 310027 , People's Republic of China. FAU - Hu, Xi AU - Hu X AD - Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences , Zhejiang University , Hangzhou 310058 , People's Republic of China. FAU - Sun, Xiaochen AU - Sun X AD - Guangxi Key Laboratory of Regenerative Medicine , Guangxi Medical University , Guangxi 530021 , People's Republic of China. FAU - He, Wenxin AU - He W AD - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , People's Republic of China. FAU - Cao, Xiankun AU - Cao X AD - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , People's Republic of China. FAU - Ling, Daishun AU - Ling D AUID- ORCID: 0000-0002-9977-0237 AD - Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences , Zhejiang University , Hangzhou 310058 , People's Republic of China. AD - MOE Key Laboratory of Biomedical Engineering, College of Biomedical Engineering and Instrument Science , Zhejiang University , Hangzhou 310058 , People's Republic of China. FAU - Li, Qian AU - Li Q AD - School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China. FAU - Fan, Chunhai AU - Fan C AUID- ORCID: 0000-0002-7171-7338 AD - School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China. FAU - Yang, Chi AU - Yang C AD - Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , People's Republic of China. FAU - Kong, Xueqian AU - Kong X AUID- ORCID: 0000-0002-1901-9073 AD - Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry , Zhejiang University , Hangzhou 310027 , People's Republic of China. FAU - Qin, An AU - Qin A AUID- ORCID: 0000-0002-8785-8848 AD - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200114 PL - United States TA - Nano Lett JT - Nano letters JID - 101088070 RN - 0 (Bone Density Conservation Agents) RN - 0 (Diphosphonates) RN - 0 (Metal-Organic Frameworks) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (cytosine-phosphorothioate guanine) RN - 6XC1PAD3KF (Zoledronic Acid) SB - IM MH - Animals MH - Bone Density Conservation Agents/chemistry/pharmacology MH - Bone Neoplasms/*drug therapy/pathology/secondary MH - Breast Neoplasms/*drug therapy/pathology MH - Cell Line, Tumor MH - Diphosphonates/chemistry/pharmacology MH - Female MH - Humans MH - Metal-Organic Frameworks/chemistry/*pharmacology MH - Mice MH - Nanoparticles/*chemistry MH - Oligodeoxyribonucleotides/chemistry/pharmacology MH - Osteoclasts/drug effects MH - Osteolysis/drug therapy/pathology MH - Tumor-Associated Macrophages/drug effects MH - Zoledronic Acid/chemistry/pharmacology OTO - NOTNLM OT - Bone targeting OT - breast cancer metastasis OT - immunostimulatory OT - metal-organic frameworks OT - osteoclast EDAT- 2020/01/10 06:00 MHDA- 2021/01/05 06:00 CRDT- 2020/01/10 06:00 PHST- 2020/01/10 06:00 [pubmed] PHST- 2021/01/05 06:00 [medline] PHST- 2020/01/10 06:00 [entrez] AID - 10.1021/acs.nanolett.9b02916 [doi] PST - ppublish SO - Nano Lett. 2020 Feb 12;20(2):829-840. doi: 10.1021/acs.nanolett.9b02916. Epub 2020 Jan 14.