Bisphosphonate type-dependent cell viability suppressive effects of carbon nanohorn-calcium phosphate-bisphosphonate nanocomposites
Bisphosphonate type-dependent cell viability suppressive effects of carbon nanohorn-calcium phosphate-bisphosphonate nanocomposites
复制标题
DOI：
10.1039/d2bm00822j
复制
发表时间：
2022-09-08
影响因子：
6.6
通讯作者：
Yudasaka, Masako
中科院分区：
文献类型：
--
作者：
Nakamura, Maki;Ueda, Katsuya;Yudasaka, Masako
在骨转移过程中，肿瘤细胞扩散至骨骼，激活破骨细胞，引起病理性骨质吸收和破坏。双膦酸盐 (BP) 抑制破骨细胞活化以吸收骨，从而减轻骨痛和骨折。我们之前开发了一种纳米复合材料，通过将 BP 化合物伊班膦酸盐负载到下一代药物载体氧化碳纳米角 (OxCNHs) 上，使用磷酸钙 (CaPs) 作为介体生成 OxCNH-CaP-BP 纳米复合材料，用于潜在的骨转移局部治疗。本研究的目的是确定由两种BP（唑来膦酸盐和帕米膦酸盐）构建的纳米复合材料的形成和生物特性。使用小鼠巨噬细胞（RAW264.7 细胞）和从 RAW264.7 细胞分化的破骨细胞进行的体外测试表明，所得的 OxCNH-CaP-BP 纳米复合材料以 BP 类型依赖性方式抑制细胞活力，并且比单独的 OxCNH 或 BP 更有效。还讨论了 OxCNH-CaP-BP 纳米复合材料基于其相对细胞摄取和活性氧生成对细胞活力的有效且 BP 类型依赖性抑制的机制。本研究支持这样的结论：BPs可以使用CaPs作为介体负载到OxCNHs上，并且OxCNH-CaP-BP纳米复合材料是用于局部治疗转移性骨破坏的假定药物。
In the process of bone metastasis, tumor cells spread to the bones to activate osteoclasts, which cause pathological bone resorption and destruction. Bisphosphonates (BPs) inhibit osteoclast activation to resorb bone, reducing bone pain and fracture. We previously developed a nanocomposite for potential localized treatment of bone metastasis by loading a BP compound, ibandronate, onto oxidized carbon nanohorns (OxCNHs), a next-generation drug carrier, using calcium phosphates (CaPs) as mediators to generate OxCNH-CaP-BP nanocomposites. The objective of the present study was to determine nanocomposite formation and biological properties of nanocomposites constructed from two BPs, zoledronate and pamidronate. In vitro tests using murine macrophages (RAW264.7 cells) and osteoclasts differentiated from RAW264.7 cells revealed that the resulting OxCNH-CaP-BP nanocomposites suppressed cell viability in a BP type-dependent manner and more effectively than OxCNHs or BPs alone. The mechanism for the potent and BP type-dependent suppression of cell viability by OxCNH-CaP-BP nanocomposites, based on their relative cellular uptake and reactive oxygen species generation, is also discussed. The present study supports the conclusions that BPs can be loaded onto OxCNHs using CaPs as mediators, and that OxCNH-CaP-BP nanocomposites are putative medicines for localized treatment of metastatic bone destruction.