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Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis.
Nano Letters ( IF 9.6 ) Pub Date : 2020-01-09 , DOI: 10.1021/acs.nanolett.9b02916 Yichuan Pang 1 , Yao Fu 2 , Chen Li 3 , Zuoxing Wu 3 , Weicheng Cao 2 , Xi Hu 4 , Xiaochen Sun 3 , Wenxin He 5 , Xiankun Cao 5 , Daishun Ling 4, 6 , Qian Li 7 , Chunhai Fan 7 , Chi Yang 1 , Xueqian Kong 2 , An Qin 5
Nano Letters ( IF 9.6 ) Pub Date : 2020-01-09 , DOI: 10.1021/acs.nanolett.9b02916 Yichuan Pang 1 , Yao Fu 2 , Chen Li 3 , Zuoxing Wu 3 , Weicheng Cao 2 , Xi Hu 4 , Xiaochen Sun 3 , Wenxin He 5 , Xiankun Cao 5 , Daishun Ling 4, 6 , Qian Li 7 , Chunhai Fan 7 , Chi Yang 1 , Xueqian Kong 2 , An Qin 5
Affiliation
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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.
中文翻译：
金属有机骨架纳米颗粒，用于改善乳腺癌相关的溶骨作用。
乳腺癌向骨的转移对治疗策略的管理提出了重大挑战。骨微环境，转移性肿瘤细胞，破骨细胞和肿瘤相关的巨噬细胞（TAM）在创造有利于转移性肿瘤的增殖，进展和生存的环境中起着至关重要的协同作用，从而反过来诱导破骨细胞介导的骨骼破坏。在这项研究中，我们通过用FDA批准的抗吸收性双膦酸盐，唑来膦酸（ZOL）进行表面修饰，对具有骨靶向能力的免疫刺激性胞嘧啶-磷酸-鸟苷（CpG）负载的金属-有机骨架（MOF）纳米粒子进行了功能化。功能化的骨靶向免疫刺激性MOF（BT-isMOF）纳米粒子在体外显示出与磷酸钙的强结合，并且在体内在骨组织中表现出特异性的靶向和积累。体外细胞和生化分析表明，BT-isMOF纳米颗粒可有效抑制破骨细胞形成，并同时诱导巨噬细胞向M1促炎表型极化。最后，使用乳癌乳腺癌骨转移的鼠内模型，我们发现BT-isMOF纳米颗粒的施用显着抑制了破骨细胞介导的骨破坏，并增强了肿瘤驻留巨噬细胞向M1表型的极化。一起，
更新日期：2020-01-15
中文翻译：
金属有机骨架纳米颗粒，用于改善乳腺癌相关的溶骨作用。
乳腺癌向骨的转移对治疗策略的管理提出了重大挑战。骨微环境，转移性肿瘤细胞，破骨细胞和肿瘤相关的巨噬细胞（TAM）在创造有利于转移性肿瘤的增殖，进展和生存的环境中起着至关重要的协同作用，从而反过来诱导破骨细胞介导的骨骼破坏。在这项研究中，我们通过用FDA批准的抗吸收性双膦酸盐，唑来膦酸（ZOL）进行表面修饰，对具有骨靶向能力的免疫刺激性胞嘧啶-磷酸-鸟苷（CpG）负载的金属-有机骨架（MOF）纳米粒子进行了功能化。功能化的骨靶向免疫刺激性MOF（BT-isMOF）纳米粒子在体外显示出与磷酸钙的强结合，并且在体内在骨组织中表现出特异性的靶向和积累。体外细胞和生化分析表明，BT-isMOF纳米颗粒可有效抑制破骨细胞形成，并同时诱导巨噬细胞向M1促炎表型极化。最后，使用乳癌乳腺癌骨转移的鼠内模型，我们发现BT-isMOF纳米颗粒的施用显着抑制了破骨细胞介导的骨破坏，并增强了肿瘤驻留巨噬细胞向M1表型的极化。一起，
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