“远程释药可控性”骨靶向纳米载药系统介导雌激素治疗绝经后骨质疏松症的实验研究

Hormone replacement therapy (HRT) was once the preferred solution to treat postmenopausal osteoporosis (PMOP). However, the estrogen has poor tissue selectivity which increase the risk of women's endometrial cancer, breast cancer, deep vein thrombosis and other diseases. If we can import estrogen (or SERMS) targeting to bone tissue and make it play a role only in the bone marrow microenvironment, it would be bound to reduce the toxic effects to non-bone tissue or organ. Our previous study found that drug and magnetic nanoparticles can be co-loaded in PLGA nanoparticles. Based on the magnetic properties of the nanoparticles, the nanoparticles can achieve magnetic induction heating because of the Nile effect and Brownian motion under an external magnetic field. And the drug release can be controlled by the regulation of the intensity of the induced magnetic field. . This study is aiming at, based on our previous work, making the estrogen and magnetic nanoparticles entrapped in PLGA nanoparticles together and bone-targeting modified using alendronate (AL) with chemical bonds. Then we build a "remote controllable drug release" bone-targeted multi-functional drug-loaded system. Under an added magnetic field, control the release of estrogen in the bone marrow microenvironment by means of changing the frequency and intensity, thus realizing the remote control of drug release for bone-targeted therapy of osteoporosis.

雌激素替代疗法是治疗绝经后骨质疏松症(PMOP)的有效方案，但雌激素的作用选择性差，副作用大。如能将雌激素(或SERMS)靶向性的导入骨组织，使其仅在骨髓微环境发挥作用，必将减少其对非骨组织或器官的毒副作用。我们前期研究发现，将药物与磁性纳米粒共同包载于PEG-PLGA纳米粒中，根据纳米粒的磁性能，在外加磁场作用下，由于耐尔效应及布朗运动可以实现纳米粒的磁感应加热。而通过对感应磁场强度的调控，可实现药物释放的“远程可控”。.本课题拟在前期工作基础上，将雌激素与磁性纳米粒共同包载于PEG-PLGA纳米粒中，利用具有主动骨靶向作用的阿仑膦酸钠(AL)对纳米载体进行骨靶向修饰，从而构建一种 “可避免RES吞噬”、能主动靶向及“释药远程可控”的多功能载药纳米粒。通过改变体外磁场的频率及强度调控体内雌激素在骨髓微环境的释放，从而实现骨质疏松症的可控性骨靶向治疗，为骨质疏松症的药物靶向治疗提供新思路。

雌激素替代疗法是治疗绝经后骨质疏松症(PMOP)的有效方案，但雌激素的作用选择性差，副作用大。如能将雌激素(或SERMS)靶向性的导入骨组织，使其仅在骨髓微环境发挥作用，必将减少其对非骨组织或器官的毒副作用。我们前期研究发现，将药物与磁性纳米粒共同包载于PEG-PLGA纳米粒中，根据纳米粒的磁性能，在外加磁场作用下，由于耐尔效应及布朗运动可以实现纳米粒的磁感应加热。而通过对感应磁场强度的调控，可实现药物释放的“远程可控”。本课题在前期工作基础上，将雌激素与磁性纳米粒共同包载于PEG-PLGA纳米粒中，利用具有主动骨靶向作用的阿仑膦酸钠(AL)对纳米载体进行骨靶向修饰，从而构建了一种“可避免RES吞噬”、能主动靶向及“释药远程可控”的多功能载药纳米粒。通过改变体外磁场的频率及强度调控体内雌激素在骨髓微环境的释放，实现了骨质疏松症的可控性骨靶向治疗，为骨质疏松症的药物靶向治疗提供了新思路。