CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People's Republic of China.
University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Nanotechnology. 2023 Dec 1;35(7). doi: 10.1088/1361-6528/ad0dc9.
The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Sim. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.
尽管在治疗效果方面，合成代谢药物在理论上优于抗吸收药物，但由于其有限的选择，限制了它们在骨质疏松症治疗中的应用潜力。作为一种流行的策略，纳米递药系统可以为合成代谢药物提供更广泛的选择。在这项研究中，设计并制备了具有骨膜靶向能力的同时掺入了辛伐他汀（Sim）的磷酸钙纳米复合材料，用于骨质疏松症的治疗。羧甲基葡聚糖（CMD）作为一种带负电荷和亲水性葡聚糖衍生物，用于稳定 CaP。此外，进一步将骨膜靶向肽（SDSSD）接枝到 CMD 上，以实现骨靶向功能。在一步配位组装策略中，疏水性合成代谢药物 Sim 和 SDSSD-CMD 接枝物（SDSSD-CMD）被掺入到 CaP 纳米颗粒中，形成 SDSSD@CaP/Sim 纳米复合材料。所得的 SDSSD@CaP/Sim 具有均匀的尺寸、良好的短期稳定性和优异的生物相容性。此外，SDSSD@CaP/Sim 表现出 Sim 的释放速率降低，呈现出缓释行为。正如预期的那样，纳米复合材料在细胞和动物研究中均表现出骨结合能力。此外，与直接注射 Sim 相比，SDSSD@CaP/Sim 实现了明显增强的骨质疏松症治疗效果。因此，我们的研究结果强调了掺入 SDSSD 和基于 CaP 的纳米复合材料作为增强合成代谢药物治疗骨质疏松症疗效的可行策略的潜力。
