A novel nano delivery system targeting different stages of osteoclasts

Bongsong Zhang; Juzhi Zhao; Hongji Yan; Yufang Zhao; Hui Tian; Cao Wang; Ruiqi Wang; Jiaming Jin; Yue Chen; Chaofan Yang; Chunfeng LI; Yanwen Jiao; Kaipeng Zheng; Fuxing Zhu; Weiming Tian

doi:10.1039/D2BM00076H

A novel nano delivery system targeting different stages of osteoclasts†

Bongsong Zhang,

^a Juzhi Zhao,^a Hongji Yan,

^bcd Yufang Zhao,^ae Hui Tian,^a Cao Wang,^a Ruiqi Wang,^a Jiaming Jin,^a Yue Chen,^a Chaofan Yang,^a Chunfeng LI,^a Yanwen Jiao,^a Kaipeng Zheng,^a Fuxing Zhu^a and Weiming Tian

*^a

Author affiliations

* Corresponding authors

^a School of Life Science and Technology, Harbin Institute of Technology, 150080 Harbin, China
E-mail: tianweiming@hit.edu.cn

^b Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm, Sweden

^c AIMES—Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden

^d Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden

^e Laboratory for Space Environment and Physical Sciences, Harbin Institute of Technology, 150080 Harbin, China

Abstract

Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist. Therefore, we designed two dual-targeting nanoparticles to target OCs at different functional stages. Using the calcitonin gene-related peptide receptor (CGRPR), which OC precursors highly express, and specific TRAPpeptides screened in the bone resorption lacuna, where mature OCs function, respectively, two types of dual-targeted nanoparticles were constructed. Afterwards, nanoparticles were grafted with hyaluronic acid (HA), which specifically binds to CD44 on the surface of the OCs. In vivo and in vitro experiments show that both nanoparticles have noticeable targeting effects on OCs. This suggests that dual-targeting nanoparticles designed for different functional periods of OC can be well targeted to the corresponding OC, and further promote the more precise delivery of drugs used to treat OP.

Biomaterials Science

A novel nano delivery system targeting different stages of osteoclasts†

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