Metal-polyDNA Nanoparticles Reconstruct Osteoporotic Microenvironment for Enhanced Osteoporosis Treatment

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Aug 2

PMID 37531423

Authors

Xueliang Liu

Fan Li

Ziliang Dong

Chao Gu

Dongsheng Mao

Jingqi Chen

Lei Luo

Yuting Huang

Jie Xiao

Zhanchun Li

Zhuang Liu

Yu Yang

Affiliations

Soon will be listed here.

Abstract

Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

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