State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2186-2197. doi: 10.1021/acsbiomaterials.0c00195. Epub 2020 Mar 24.
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.
双膦酸盐（BPs）被常规用于治疗代谢性骨疾病。为避免长期使用双膦酸盐带来的不良副作用并提高其在骨微环境中的生物利用度，我们最初通过一步合成法将利塞膦酸钠（RIS）分子封装在纳米沸石咪唑酯骨架-8 颗粒（nZIF-8）中，生成 RIS@ZIF-8 纳米颗粒。RIS@ZIF-8 纳米颗粒表现出高载药包封效率（64.21±2.48%）、良好的生物相容性、可控的药物释放能力以及促进骨再生的双重作用。这项工作探索了 RIS@ZIF-8 纳米颗粒的潜力，其不仅可以增强 ATP 生成、诱导细胞外基质（ECM）矿化和上调成骨基因的表达水平，还可以有效抑制多核巨细胞的形成并降低 Rankl/Opg 比值。总之，RIS@ZIF-8 纳米颗粒可能是一种很有前途的方法，可以协同增强骨再生的成骨和抗吸收特性，可用于局部治疗骨缺损。
