此前，我们表明，当唑来膦酸盐（ZOL）（一种双膦酸盐）用作包含ZOL（一种“球形氧化单壁碳纳米角（OxCNH）”和磷酸钙（CaP）。这种纳米复合材料被称为 OxCNH-CaP-ZOL，是治疗与转移性骨癌相关的骨脆性患者的潜在治疗剂。由于 OxCNH-CaP-ZOL 含有构成 CaP-ZOL 纳米复合材料的副产物，因此本研究的目的是制备不含此类副产物的更复杂的纳米复合材料；这是通过在制备过程中减少钙离子和磷酸根离子的可用性来实现的。在这种新型纳米复合材料中，ZOL 负载到 OxCNH 上是由 Ca 介导的，因此它被称为 OxCNH-Ca-ZOL。由于 OxCNH-Ca-ZOL 中的 ZOL 量约为 OxCNH-CaP-ZOL 中的一半，并且小鼠巨噬细胞（RAW264.7 细胞）摄取的 OxCNH-Ca-ZOL 比 OxCNH-CaP-ZOL 少，因此内部 ZOL 的量暴露于OxCNH-Ca-ZOL的RAW264.7细胞少于暴露于OxCNH-CaP-ZOL的细胞内部。尽管存在这一缺点，OxCNH-Ca-ZOL 对 RAW264.7 细胞的活力具有类似于 OxCNH-CaP-ZOL 的抑制作用。这些现象的原因尚不清楚；然而，这可能是由于 OxCNH-Ca-ZOL 和 OxCNH-CaP-ZOL 之间的 ZOL 释放速率不同所致。此外，通过将 RANKL 与 OxCNH-Ca-ZOL 共同给药，与 OxCNH-CaP-ZOL 一样有效地抑制核因子 kappa-B 配体 (RANKL) 受体激活剂诱导的 RAW264.7 细胞分化为破骨细胞，并且事实上，它们的效果比免费的 ZOL 还要大。

Previously, we showed that the anti-osteoclast effect of zoledronate (ZOL), a type of bisphosphonate, is enhanced when it is used as a nanocomposite comprising ZOL, an "oxidized single-walled carbon nanohorn (OxCNH) with a spherical shape" and calcium phosphate (CaP). This nanocomposite, termed OxCNH-CaP-ZOL, is a potential therapeutic agent for patients with bone fragility associated with metastatic bone cancer. Because OxCNH-CaP-ZOL contains by-products that comprise CaP-ZOL nanocomposites, the aim of this study was to prepare more sophisticated nanocomposites lacking such by-products; it was achieved by reducing the availability of calcium and phosphate ions during the preparation process. In this new nanocomposite, ZOL loading onto OxCNH was mediated by Ca, and therefore it is referred to as OxCNH-Ca-ZOL. Because the amount of ZOL in OxCNH-Ca-ZOL was about half that in OxCNH-CaP-ZOL and murine macrophages (RAW264.7 cells) took up less OxCNH-Ca-ZOL than OxCNH-CaP-ZOL, the amount of ZOL inside RAW264.7 cells exposed to OxCNH-Ca-ZOL was less than that inside cells exposed to OxCNH-CaP-ZOL. Despite this drawback, OxCNH-Ca-ZOL had suppressive effects similar to OxCNH-CaP-ZOL on the viability of RAW264.7 cells. The reason for these phenomena is not clear; however, it could be due to the differences in the ZOL release rate between OxCNH-Ca-ZOL and OxCNH-CaP-ZOL. In addition, receptor activator of nuclear factor kappa-B ligand (RANKL)-induced differentiation of RAW264.7 cells into osteoclasts was suppressed by co-administration of RANKL with OxCNH-Ca-ZOL as effectively as with OxCNH-CaP-ZOL, and indeed, their effects were greater than those of free ZOL.