Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Nano Lett. 2021 Oct 13;21(19):7998-8007. doi: 10.1021/acs.nanolett.1c02150. Epub 2021 Sep 16.
With the aging of the population, postmenopausal osteoporosis becomes increasingly widespread and severe as fractures caused by osteoporosis may lead to permanent disabilities and even death. Inspired by extracellular vesicles that participate in bone remodeling, we present a biomimicking polymer vesicle for bone-targeted β-estradiol (E) delivery. This vesicle is self-assembled from a poly(ε-caprolactone)--poly[(l-glutamic acid)--(l-glutamic acid-alendronic acid)] (PCL--P[Glu--(Glu-ADA)]) diblock copolymer. The alendronic acid (ADA) on the coronas endows the polymer vesicles with a high bone affinity and acts synergistically with E to achieve an enhanced therapeutic effect. As confirmed with ovariectomized osteoporosis rat models, bone loss was significantly reversed as the recovery rates of total BMD (bone mineral density) and trabecular BMD were 70.4% and 99.3%, respectively. Overall, this work provides fresh insight into the treatment of osteoporosis.
随着人口老龄化，绝经后骨质疏松症变得越来越普遍和严重，因为骨质疏松症引起的骨折可能导致永久性残疾，甚至死亡。受参与骨重塑的细胞外囊泡的启发，我们提出了一种用于骨靶向β-雌二醇（E）递药的仿生聚合物囊泡。这种囊泡由聚（ε-己内酯）-聚[（l-谷氨酸）-（l-谷氨酸-阿仑膦酸）]（PCL-P[Glu-（Glu-ADA）]）两亲性嵌段共聚物自组装而成。冠部上的阿仑膦酸（ADA）赋予聚合物囊泡高骨亲和力，并与 E 协同作用，以实现增强的治疗效果。正如去卵巢骨质疏松症大鼠模型所证实的那样，骨丢失得到了显著逆转，总骨密度（BMD）和小梁骨密度的恢复率分别为 70.4%和 99.3%。总的来说，这项工作为骨质疏松症的治疗提供了新的见解。
