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<p>Bone metastases is the most common incidence in the advanced stage of breast cancer patients. In clinic, chemotherapeutic drugs and anti-resorptive drugs are used to suppress cancer cell and osteoclast activity for the decreased incidence of bone-related events. However, the progression-free and 5-year survival rate is still very low in patients with breast cancer bone metastasis. Once bone metastasis occurs, tumor cells disrupt the bone microenvironment’s balance, causing osteolytic lesions and strengthening tumor cell stemness to accelerate metastasis. Therefore, addressing the complexity of bone microenvironment, this work developed new targeted therapeutic nanocomposites 20%Sr/HAP@CS@miR34a for breast cancer bone metastasis. The twenty-percentage strontium-doped hydroxyapatite nanoparticles (20%Sr/HAP) were prepared by hydrothermal method and had the ability to promote osteogenic differentiation and inhibit osteoclast differentiation. The nanocomposites 20%Sr/HAP@CS@miR34a was constructed by modifying chitosan and loading miR34a. 20%Sr/HAP@CS showed safe and bone-targeting capacity in mice after intravenous injection. 20%Sr/HAP@CS@miR34a weakened the stemness of breast cancer cells and decreased invasion and metastasis. 20%Sr/HAP@CS@miR34a also suppressed the formation of osteoclast-like cells in vitro and alleviated osteolysis in the 3D co-culture model of breast cancer bone metastasis. Therefore, 20%Sr/HAP@CS@miR34a nanocomposites provide a bone-targeting therapeutic strategy in the bone microenvironment for breast cancer bone metastasis.</p>

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Strontium-doped hydroxyapatite nanocomposites for breast cancer bone metastasis therapy by modulating bone formation and suppressing cancer cell stemness

  • 期刊论文

  • 发表日期：

    2025年9月16日

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  • Yanlian Lu,
  • Zhengjie Liu,
  • Mengmeng Ji,
  • Lili Ren,
  • Yanru Song,
  • Guoqiang Zhou,
  • Hua Yang,
  • Kun Ge

摘要

Bone metastases is the most common incidence in the advanced stage of breast cancer patients. In clinic, chemotherapeutic drugs and anti-resorptive drugs are used to suppress cancer cell and osteoclast activity for the decreased incidence of bone-related events. However, the progression-free and 5-year survival rate is still very low in patients with breast cancer bone metastasis. Once bone metastasis occurs, tumor cells disrupt the bone microenvironment’s balance, causing osteolytic lesions and strengthening tumor cell stemness to accelerate metastasis. Therefore, addressing the complexity of bone microenvironment, this work developed new targeted therapeutic nanocomposites 20%Sr/HAP@CS@miR34a for breast cancer bone metastasis. The twenty-percentage strontium-doped hydroxyapatite nanoparticles (20%Sr/HAP) were prepared by hydrothermal method and had the ability to promote osteogenic differentiation and inhibit osteoclast differentiation. The nanocomposites 20%Sr/HAP@CS@miR34a was constructed by modifying chitosan and loading miR34a. 20%Sr/HAP@CS showed safe and bone-targeting capacity in mice after intravenous injection. 20%Sr/HAP@CS@miR34a weakened the stemness of breast cancer cells and decreased invasion and metastasis. 20%Sr/HAP@CS@miR34a also suppressed the formation of osteoclast-like cells in vitro and alleviated osteolysis in the 3D co-culture model of breast cancer bone metastasis. Therefore, 20%Sr/HAP@CS@miR34a nanocomposites provide a bone-targeting therapeutic strategy in the bone microenvironment for breast cancer bone metastasis.