Osteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy.

骨肉瘤（OS）仍然是骨骼中最具威胁性的原发性人类恶性肿瘤之一，尤其是在生命的第一个或第二个十年中。不幸的是，在过去的四十年中，临床治疗效果没有实质性的改善。因此，为了有效地根除肿瘤，迫切需要一种预防肿瘤复发的新方法。在这里，我们开发了一种新型的双膦酸盐（BP）负载的微弧氧化（MAO）涂层镁锶（Mg-Sr）合金颗粒，可以抑制OS，并阐明了抑制作用的细胞和分子机制。为了产生这种粒料，将含氮的BP与中空Mg-Sr合金上的MAO涂层化学结合。我们证明了BP包覆的Mg药丸具有多种体外和OS疗法所需的功能体内研究。在细胞水平上，BP包被的Mg沉淀不仅在二维（2D）细胞培养环境中诱导OS细胞凋亡和坏死，以及抗肿瘤侵袭，而且还通过OS细胞系破坏多细胞肿瘤球体的形成。三维（3D）细胞培养环境。在体内水平，BP包被的Mg药丸可以破坏镁并通过协同的Mg降解和药物释放防止肿瘤复发。进一步表明，通过在分子水平上抑制甲羟戊酸途径可以实现对我们颗粒的OS的优异抑制作用。因此，这些结果共同表明，BP包被的Mg颗粒是OS治疗中去除肿瘤后修复缺损的未来应用的有希望的候选者。