Bisphosphonates (BPs) are routinely administered for the treatment of turnover bone diseases. To avoid the undesirable adverse effects of long-term usage of bisphosphonates and improve their bioavailability in the bone microenvironment, we initially encapsulated risedronate (RIS) molecules inside nanoscale zeolitic imidazolate framework-8 particles (nZIF-8) by a one-step synthesis method to generate RIS@ZIF-8 nanoparticles. RIS@ZIF-8 nanoparticles displayed high loading encapsulation efficiency (64.21 ± 2.48%), good biocompatibility, controlled drug release capacity, and dual effects for bone regeneration. This work explored the potential of RIS@ZIF-8 nanoparticles, which could not only enhance ATP production, induce extracellular matrix (ECM) mineralization, and upregulate the expression levels of osteogenic genes but also effectively inhibit the formation of multinucleated giant osteocasts and decrease the Rankl/Opg ratio. Overall, RIS@ZIF-8 nanoparticles could be a very promising approach to synergistically enhance osteogenic and antiresorptive properties for bone regeneration, which could be utilized for the local treatment of bone defects.

中文翻译：

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沸石咪唑盐Framework-8封装Risedronate协同增强骨再生的成骨和抗吸收特性。

通常使用双膦酸盐（BPs）来治疗翻新性骨疾病。为了避免长期使用双膦酸盐的不良影响并提高其在骨骼微环境中的生物利用度，我们首先通过一步合成方法将利塞膦酸盐（RIS）分子封装在纳米级沸石咪唑酯骨架8颗粒（nZIF-8）中生成RIS @ ZIF-8纳米粒子。RIS @ ZIF-8纳米颗粒显示出高的负载封装效率（64.21±2.48％），良好的生物相容性，可控的药物释放能力以及对骨再生的双重作用。这项工作探索了RIS @ ZIF-8纳米粒子的潜力，这种纳米粒子不仅可以增强ATP的产生，还可以诱导细胞外基质（ECM）矿化，并上调成骨基因的表达水平，但也有效抑制多核巨骨铸的形成并降低Rank1 / Opg比。总体而言，RIS @ ZIF-8纳米粒子可能是协同增强骨再生的成骨和抗吸收特性的非常有前途的方法，可用于局部治疗骨缺损。