title: In Vitro and in Vivo Mechanism of Bone Tumor Inhibition by Selenium-Doped Bone Mineral Nanoparticles.
abstract: Biocompatible tissue-borne crystalline nanoparticles releasing anticancer therapeutic inorganic elements are intriguing therapeutics holding the promise for both tissue repair and cancer therapy. However, how the therapeutic inorganic elements released from the lattice of such nanoparticles induce tumor inhibition remains unclear. Here we use selenium-doped hydroxyapatite nanoparticles (Se-HANs), which could potentially fill the bone defect generated from bone tumor removal while killing residual tumor cells, as an example to study the mechanism by which selenium released from the lattice of Se-HANs induces apoptosis of bone cancer cells in vitro and inhibits the growth of bone tumors in vivo. We found that Se-HANs induced apoptosis of tumor cells by an inherent caspase-dependent apoptosis pathway synergistically orchestrated with the generation of reactive oxygen species. Such mechanism was further validated by in vivo animal evaluation in which Se-HANs tremendously induced tumor apoptosis to inhibit tumor growth while reducing systemic toxicity. Our work proposes a feasible paradigm toward the design of tissue-repairing inorganic nanoparticles that bear therapeutic ions in the lattice and can release them in vivo for inhibiting tumor formation.
authors: Yifan
authors: Y
authors: Wang
authors: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors: Jianglin
authors: J
authors: Wang
authors: Hang
authors: H
authors: Hao
authors: Mingle
authors: M
authors: Cai
authors: Shiyao
authors: S
authors: Wang
authors: Jun
authors: J
authors: Ma
authors: Department of Oncology, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan 430071, China.
authors: Yan
authors: Y
authors: Li
authors: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma 73019, United States.|School of Materials Science and Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, China.
authors: Chuanbin
authors: C
authors: Mao
authors: Shengmin
authors: S
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D017886:Durapatite; D053758:Nanoparticles; D017382:Reactive Oxygen Species; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D017886:Durapatite; D012643:Selenium
keywords: apoptosis; nanoparticles; osteosarcoma; selenium; tumor inhibition