Kameda Yuka, Aizawa Mamoru, Sato Taira, Honda Michiyo
Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Kanagawa, Japan.
Organization for the Strategic Coordination of Research and Intellectual Properties, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Kanagawa, Japan.
Int J Mol Sci. 2021 Feb 14;22(4):1889. doi: 10.3390/ijms22041889.
Osteosarcoma has a poor survival rate due to relapse and metastasis. Zoledronic acid (ZOL), an anti-resorptive and anti-tumor agent, is used for treating osteosarcoma. Delivery of ZOL to the target region is difficult due to its high binding affinity to bone minerals. This study developed a novel treatment for osteosarcoma by delivering ZOL to the target region locally and sustainably. In this study, we fabricated a novel bone substitute by loading ZOL on β-tricalcium phosphate (β-TCP). The ZOL-loaded β-TCP (ZOL/β-TCP) would be expected to express the inhibitory effects via both bound-ZOL (bound to β-TCP) and free-ZOL (release from ZOL/β-TCP). To explore the ability to release ZOL from the ZOL/β-TCP, the amount of released ZOL was measured. The released profile indicates that a small amount of ZOL was released, and most of it remained on the β-TCP. Our data showed that ZOL/β-TCP could successfully express the effects of ZOL via both bound-ZOL and free-ZOL. In addition, we examined the biological effects of bound/free-ZOL using osteosarcoma and osteoclasts (target cells). The results showed that two states of ZOL (bound/free) inhibit target cell activities. As a result, ZOL/β-TCP is a promising candidate for application as a novel bone substitute.
骨肉瘤由于复发和转移，生存率较低。唑来膦酸（ZOL）是一种抗骨吸收和抗肿瘤药物，用于治疗骨肉瘤。由于ZOL与骨矿物质的高结合亲和力，将其递送至靶区域较为困难。本研究通过将ZOL局部且持续地递送至靶区域，开发了一种治疗骨肉瘤的新方法。在本研究中，我们通过将ZOL负载于β-磷酸三钙（β-TCP）上制备了一种新型骨替代物。负载ZOL的β-TCP（ZOL/β-TCP）有望通过结合态ZOL（结合于β-TCP）和游离态ZOL（从ZOL/β-TCP释放）发挥抑制作用。为了探究ZOL从ZOL/β-TCP中的释放能力，我们测量了释放的ZOL量。释放曲线表明，只有少量ZOL释放，大部分仍保留在β-TCP上。我们的数据表明，ZOL/β-TCP能够通过结合态ZOL和游离态ZOL成功发挥ZOL的作用。此外，我们使用骨肉瘤细胞和破骨细胞（靶细胞）检测了结合态/游离态ZOL的生物学效应。结果表明，两种状态的ZOL（结合态/游离态）均能抑制靶细胞活性。因此，ZOL/β-TCP作为一种新型骨替代物具有广阔的应用前景。
