Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer

• Published in: Nanomedicine 2019-10, Vol.21, p.102054-102054, Article 102054
• Main Authors: Bai, Shao-bo, Liu, Dao-zhou, Cheng, Ying, Cui, Han, Liu, Miao, Cui, Min-xuan, Zhang, Bang-le, Mei, Qi-bing, Zhou, Si-yuan
• Format: Article
• Language: English
• Subjects: Bone metastases of lung cancer; Docetaxel; Hyaluronic acid; Osteoclasts; PAMAM
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2019.102054

Bone is one of the prone metastatic sites of lung cancer. Osteoclast plays an important role in bone resorption and the growth of bone metastases of lung cancer. In order to treat bone metastases of lung cancer, we reported a docetaxel (DTX)-loaded nanoparticle, DTX@AHP, which could target dually at osteoclasts and bone metastatic tumor cells. The in vitro drug release from DTX@AHP exhibited pH and redox responsive characteristics. DTX@AHP displayed high binding affinity with bone matrix. In addition, DTX@AHP significantly inhibited the differentiation of RAW264.7 into osteoclast and effectively inhibited the proliferation of osteoclasts and tumor cells in in-vitro 3D bone metastases model of lung cancer. DTX@AHP could accumulate in bone metastases sites in vivo. Consequently, DTX@AHP not only markedly inhibited the growth of bone metastases of lung cancer but also reduced osteolysis in tumor-bearing mice. DTX@AHP exhibited great potential in the treatment of bone metastases of lung cancer. Bone-targeted nanoparticles respectively deliver alendronate (ALN) and docetaxel (DTX) to osteoclasts and tumor cells of bone metastases, subsequently inhibiting the activation of osteoclasts and the growth of bone metastases of lung cancer. The osteolytic bone destruction is also attenuated. [Display omitted]