Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China.
J Nanobiotechnology. 2024 Apr 5;22(1):153. doi: 10.1186/s12951-024-02412-9.
Osteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting osteoclast-mediated bone resorption. The limited water solubility and lack of targeting specificity hinder the effective accumulation of Oroxylin A within the pathological environment of osteoporosis.
Osteoclasts' microenvironment-responsive nanoparticles are prepared by incorporating Oroxylin A with amorphous calcium carbonate (ACC) and coated with glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing the drug delivery efficiency as well as therapeutic effect. The obtained smart nanoparticles, coined as OAPLG, could instantly neutralize acid and release Oroxylin A in the extracellular microenvironment of osteoclasts. The combination of Oroxylin A and ACC synergistically inhibits osteoclast formation and activity, leading to a significant reversal of systemic bone loss in the ovariectomized mice model.
The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.
骨质疏松症的特征是骨内稳态失衡，导致由于破骨细胞过度活跃介导的酸化微环境，骨矿物质过度溶解。木犀草素 A（ORO）是一种天然黄酮类化合物，通过抑制破骨细胞介导的骨吸收，显示出逆转骨质疏松症的潜力。有限的水溶性和缺乏靶向特异性阻碍了 Oroxylin A 在骨质疏松症病理环境中的有效积累。
通过将 Oroxylin A 与无定形碳酸钙（ACC）结合，并涂以上谷氨酸六肽修饰的磷脂，制备了破骨细胞微环境响应性纳米颗粒，旨在增强药物递送效率和治疗效果。所得智能纳米颗粒，称为 OAPLG，可在破骨细胞细胞外微环境中即时中和酸并释放 Oroxylin A。Oroxylin A 和 ACC 的组合协同抑制破骨细胞的形成和活性，导致去卵巢小鼠模型中全身骨丢失的显著逆转。
该工作强调了一种基于 ACC 的智能纳米平台，用于亲脂性药物的时空控制释放，并说明了其在治疗骨质疏松症方面的显著治疗潜力。
