Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan.
Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
ACS Appl Mater Interfaces. 2021 Jan 27;13(3):3701-3712. doi: 10.1021/acsami.0c20923. Epub 2021 Jan 6.
Carbon nanohorns (CNHs), a type of nanocarbon, have been studied for the application of drug delivery systems (DDSs) because they are easily functionalized, support bone regeneration, can be used to perform photohyperthermia, have low toxicity, and are easily phagocytosed by macrophages. To take advantage of these features of CNHs, we developed a DDS for the local treatment of bone metastasis by loading the antibone resorption drug ibandronate (IBN) onto CNHs. The poor adsorption of IBN onto CNHs due to the weak hydrophilic-hydrophobic interaction was overcome by using calcium phosphates (CaPs) as mediators. In the fabrication process, we used oxidized CNH (OxCNH), which is less hydrophobic, onto which IBN was coprecipitated with CaP from a labile supersaturated CaP solution. OxCNH-CaP-IBN composite nanoparticles exerted stronger cell-suppressive effects than OxCNH and IBN in both murine macrophages (RAW264.7 cells) and osteoclasts (differentiated from RAW264.7 cells). OxCNH-CaP-IBN composite nanoparticles were efficiently phagocytosed by macrophage cells, where they specifically accumulated in lysosomes. The stronger cell-suppressive effects were likely due to intracellular delivery of IBN, i.e., the release of IBN from OxCNH-CaP-IBN composite nanoparticles via dissociation of CaP in the acidic environment of lysosomes. Our findings suggest that OxCNH-CaP-IBN composite nanoparticles are potentially useful for the local treatment of metastatic bone destruction.
碳纳米角（CNHs）是一种纳米碳，因其易于功能化、支持骨再生、可用于光热疗、毒性低且易被巨噬细胞吞噬等特点，已被研究用于药物传递系统（DDS）。为了利用 CNHs 的这些特性，我们开发了一种用于局部治疗骨转移的 DDS，即将抗骨吸收药物伊班膦酸盐（IBN）负载到 CNHs 上。由于弱亲水-疏水相互作用，IBN 对 CNHs 的吸附不良，通过使用磷酸钙（CaP）作为介导物来克服。在制备过程中，我们使用氧化的 CNH（OxCNH），其疏水性较低，将 IBN 与 CaP 共沉淀从不稳定的过饱和 CaP 溶液中。OxCNH-CaP-IBN 复合纳米颗粒在小鼠巨噬细胞（RAW264.7 细胞）和破骨细胞（从 RAW264.7 细胞分化而来）中的细胞抑制作用均强于 OxCNH 和 IBN。OxCNH-CaP-IBN 复合纳米颗粒被巨噬细胞细胞有效吞噬，其中它们特异性地积聚在溶酶体中。更强的细胞抑制作用可能是由于 IBN 的细胞内递呈，即通过溶酶体酸性环境中 CaP 的解离，从 OxCNH-CaP-IBN 复合纳米颗粒中释放 IBN。我们的研究结果表明，OxCNH-CaP-IBN 复合纳米颗粒可能对局部治疗转移性骨破坏有用。
