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

  • Small. 2023 Mar 27;e2207195. doi: 10.1002/smll.202207195.
Haojun Liang  1 ,  Kui Chen  2 ,  Jing Xie  3 ,  Lei Yao  2 ,  Yunpeng Liu  2 ,  Fan Hu  1 ,  Hao Li  1 ,  Yinze Lei  3 ,  Yujiao Wang  2 ,  Linwen Lv  2 ,  Ziteng Chen  2 ,  Sen Liu  2 ,  Qiuyang Liu  2 ,  Zhijie Wang  2 ,  Jiacheng Li  2 ,  Ya-Nan Chang  2 ,  Juan Li  2 ,  Hui Yuan  2 ,  Gengyan Xing  2 ,  Gengmei Xing  1
Affiliations
  • 1. Department of Orthopedic, The Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100039, P. R. China.
  • 2. Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100043, P. R. China.
  • 3. State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing, 100081, P. R. China.
PMID: 36971278 DOI: 10.1002/smll.202207195
Abstract

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.

Keywords
local treatments; osteoblast-osteoclast communication; osteoporosis; radial extracorporeal shockwaves; stimulus-responsive nano-drug delivery systems.
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