文献：A Bone-Penetrating Precise Controllable Drug Release System Enables Localized Treatment of Osteoporotic Fracture Prevention via Modulating Osteoblast-Osteoclast Communication

文献链接：https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202207195

作者：Haojun Liang, Kui Chen, Jing Xie, Lei Yao, Yunpeng Liu, Fan Hu, Hao Li, Yinze Lei, Yujiao Wang, Linwen Lv, Ziteng Chen, Sen Liu, Qiuyang Liu, Zhijie Wang, Jiacheng Li, Ya-Nan Chang, Juan Li, Hui Yuan, Gengyan Xing, Gengmei Xing

相关产品：phos-PEG-OH （磷酸化聚乙二醇-羧基）

原文摘要：

Improving local bone mineral density (BMD) at fracture-prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano-drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)-contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co-culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro-osteoblasts mineralization results are achieved via maintaining osteoblast-osteoclast (OB-OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone-related parameters and mechanical properties in the ovariectomy (OVX)-induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW-responsive NDDS can effectively improve local BMD in OP therapy.  

phos-PEG-OH:通常是指一种含有磷酸基团（phos）、聚乙二醇（PEG）和羟基（OH）的化合物。其中，聚乙二醇（PEG）是一个由乙二醇单体重复聚合而成的长链聚合物，它具有良好的亲水性和生物相容性。磷酸基团可以为分子提供一些特殊的化学性质，如与金属离子的结合能力等。羟基则是一个具有反应活性的官能团，可以参与多种化学反应，如酯化反应、醚化反应等。基于phos-PEG-OH的性能，纳米化合物递送系统（NDDS）的介绍如下：

图：聚乙二醇结构式

合成过程：

将phos - PEG - OH 和化合物按既定摩尔比置于圆底烧瓶中，加入无水二氯甲烷，用磁力搅拌器搅拌，直至两者完全溶解，得到均匀的有机相溶液。把所得有机相溶液缓慢滴加至预冷的 PBS 缓冲溶液中，缓冲溶液置于三口烧瓶，瓶内配备强力磁力搅拌装置，控制滴加速度；期间溶液会迅速变浑浊，phos - PEG - OH 与化合物因溶剂极性改变开始自组装形成纳米粒子。滴加完毕后，继续搅拌，让纳米粒子充分成型、稳定，确保化合物均匀负载于纳米粒子内部。通过高速离心机，以合适转速离心，弃去上清液，收集纳米粒子沉淀；沉淀用新鲜 PBS 缓冲溶液重悬，反复离心、洗涤，去除未负载化合物、多余 phos - PEG - OH 及有机溶剂残留。如需表面修饰，例如添加靶向配体以增强tumour靶向性，将纳米粒子与适量靶向配体（如叶酸、抗体）、交联剂在缓冲溶液中混合，温和搅拌，促使配体共价连接到纳米粒子表面；反应结束后，再次透析或离心，去除多余交联剂与配体。

结论：

该文献成功制备出基于phos-PEG-OH合成的纳米化合物递送系统（NDDS）。数据显示NDDS具有良好性能。研究发现表明，可调节且准确的 rESW 响应 NDDS 可以有效改善 OP Treatment 中的局部 BMD。