破骨细胞和肿瘤细胞双重靶向纳米颗粒治疗肺癌骨转移。
Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer.
机构信息
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University, Xi'an, China.
出版信息
Nanomedicine. 2019 Oct;21:102054. doi: 10.1016/j.nano.2019.102054. Epub 2019 Jul 13.
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.
骨是肺癌易发生转移的部位之一。破骨细胞在骨吸收和肺癌骨转移的生长中起重要作用。为了治疗肺癌骨转移，我们报道了一种载多西紫杉醇（DTX）的纳米颗粒，DTX@AHP，它可以双重靶向破骨细胞和骨转移肿瘤细胞。DTX@AHP 的体外药物释放表现出 pH 和氧化还原响应特性。DTX@AHP 与骨基质具有高结合亲和力。此外，DTX@AHP 显著抑制 RAW264.7 向破骨细胞的分化，并有效抑制体外肺癌骨转移 3D 模型中破骨细胞和肿瘤细胞的增殖。DTX@AHP 可以在体内积聚在骨转移部位。因此，DTX@AHP 不仅显著抑制了肺癌骨转移的生长，而且减少了荷瘤小鼠的溶骨性骨质破坏。DTX@AHP 在治疗肺癌骨转移方面具有很大的潜力。
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