Zeolitic Imidazolate Framework-8 Encapsulating Risedronate Synergistically Enhances Osteogenic and Antiresorptive Properties for Bone Regeneration

Zeolitic Imidazolate Framework-8 Encapsulating Risedronate Synergistically Enhances Osteogenic and Antiresorptive Properties for Bone Regeneration
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沸石咪唑框架 8 封装利塞膦酸盐可协同增强骨再生的成骨和抗吸收特性

DOI:
10.1021/acsbiomaterials.0c00195
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发表时间:
2020-04-01
影响因子:
5.8
通讯作者:
Wan, Qianbing
Wan, Qianbing
中科院分区:
工程技术2区
文献类型:
--
作者:
Cheng, Xinting;Zhu, Zhou;Wan, Qianbing

文献摘要

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双膦酸盐(BP)是治疗骨转换疾病的常规药物。为了避免长期使用双膦酸盐的不良反应并提高其在骨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)分子包封在纳米级沸石咪唑骨架-8颗粒(nZIF-8)中以产生RIS@ZIF-8纳米颗粒。RIS@ZIF-8纳米颗粒具有高载药包封率(64.21 +/- 2.48%)、良好的生物相容性、可控的药物释放能力和骨再生的双重作用。本工作探索了RIS@ZIF-8纳米颗粒的潜力,其不仅可以增强ATP产生,诱导细胞外基质(ECM)矿化,上调成骨基因的表达水平,而且还可以有效抑制多核巨大骨管型的形成并降低Rankl/Opg比值。总之,RIS@ZIF-8纳米颗粒可能是一种非常有前途的方法,可以协同增强骨再生的成骨和抗吸收特性,可用于骨缺损的局部治疗。
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.