摘要
目的研究体外冲击波(extracorporeal shock wave,ESW)响应型唑来膦酸(zoledronic acid,ZOL)钙纳米颗粒(ZOL-Ca nanoparticals,ZCNP)的制备及其靶向控释对骨质疏松骨代谢及骨量的影响。方法通过模板法以ZOL为磷源,CaCl2为钙源制备ZCNP。利用扫描电子显微镜、动态光散射对ZCNP进行表征。通过紫外可见吸收光谱及电感耦合等离子体光发射光谱法评估ZOL的负载以及载药率。利用CCK-8法检测ZCNP对鼠源骨髓单核细胞(bone marrow mononu-clear cells,BMMs)活力的影响;采用溶血实验检测ZCNP的生物相容性。通过荧光标记ZCNP对其骨靶向性进行验证。采用药物释放实验验证了ZCNP的ESW响应性。在体外,利用TRAP染色检验ZCNP的破骨抑制情况;ARS染色检验ZCNP对成骨活性的影响。在体内,利用卵巢摘除骨质疏松模型验证ZCNP对骨量的影响。结果ZCNP呈类球形结构,约60 nm。ZCNP的ZOL负载率为(59.68±1.48)%。ZCNP在0、0.01、0.1、1、10μmol/L浓度下对小鼠BMMs的细胞活性影响无明显差异(P>0.05)。ZCNP在ESW作用下可快速释放ZOL。ESW+ZCNP可抑制破骨细胞活性,促进成骨细胞增殖。ESW+ZCNP可明显提高卵巢摘除骨质疏松模型局部骨量。结论ESW响应型ZCNP可通过有效精准靶向控释,抑制破骨,促进成骨提升卵巢摘除模型局部骨量,预防骨质疏松性骨折。
Objective To study the preparation of extracorporeal shock wave(ESW)-responsive zoledronic acid(ZOL)calcium nanoparticles[ZOL-Ca nanoparticles(ZCNP)]and their effects of targeted controlled release on bone metabolism and bone mass in osteoporosis.Methods ZCNP was prepared by template method using ZOL as phosphorus source and CaCl2 as calcium source.ZCNP was characterized by scanning electron microscopy and dynamic light scattering.The loading of ZOL as well as the drug loading rate were evaluated by UV-Vis absorption spectroscopy and inductively coupled plasma photoemission spectroscopy.The effects of ZCNP on the cell viability of murine-derived bone marrow mononuclear cells(BMMs)were detected by CCK-8 assay;the biocompatibility of ZCNP was examined by hemolysis assay.The bone targeting of ZCNP was verified by fluorescent labeling.The ESW responsiveness of ZCNP was verified using drug release assay.In vitro,the osteoblastic inhibition of ZCNP was examined using TRAP staining;the effect of ZCNP on osteogenic activity was examined by ARS staining.In vivo,the effect of ZCNP on bone mass was verified using the ovariectomy(OVX)osteoporosis model.Results ZCNP has a spherical structure of about 60 nm,and the ZOL loading rate of ZCNP was(59.68±1.48)%.The effects of ZCNP on the cellular activity of mouse BMMs at the concentrations of 0,0.01,0.1,1,and 10μmol/L did not show any significant difference(P>0.05).ZCNP can release ZOL rapidly under the action of ESW.The ESW+ZCNP group inhibited osteoclast(OC)activity and promoted osteoblast(OB)proliferation.The ESW+ZCNP group significantly increased local bone mass in the OVX osteoporosis model.Conclusions ESW-responsive ZCNP can prevent osteoporotic fracture by inhibiting OB and promoting osteogenesis to enhance local bone mass in OVX model through effective and precise targeted controlled release.
作者
李浩
肖健
胡帆
王策
陈奎
邢更彦
Li Hao;Xiao Jian;Hu Fan;Wang Ce;Chen Kui;Xing Gengyan(Clinical College of the Armed Police General Hospital,The Fifth School of Clinical Medical,Anhui Medical University,Hefei 230032,Anhui,China;Department of Orthopedics,The Third Medical Center,Chinese PLA General Hospital,Beijing 100039,China;CAS Key Laboratory for Biomedical Effects of Nanomaterial&Nanosafety,Institute of High Energy Physics,Chinese Academy of Sciences,Beijing 100049,China)
出处
《中国医学前沿杂志（电子版）》
CSCD
北大核心
2024年第7期47-54,I0002,共9页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
基金
国家自然科学基金面上项目(81873914)。
关键词
体外冲击波
唑来膦酸
靶向控释
骨质疏松性骨折
Extracorporeal shock wave
Zoledronic acid
Targeted controlled release
Osteoporotic fracture
