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.

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Selenite‐doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation‐mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart.

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Large bone defect creates an urgent need for osteogenic biomaterials. However, bone nonunion and infection are choke points in the therapy of this disease. How to recruit the mesenchymal stem cells to defect sites and increase the cell viability are the critical processes. One effective method was the fabrication of biomimetic silk fibrin/selenium-doped hydroxyapatite (SF/HASe) material, which could create a niche for cell proliferation. So, the aim of the present study was to seek a facile route to prepare this biocomposites and investigate the osteogenic capability. Results showed that the biomimetic coprecipitation was a successful route to prepare SF/HASe biocomposites, which presented higher cell proliferation activity and better modulation of the selenite release during incubation in biological medium. Besides, the biocomposites exhibited weird and porous pot morphology. Such features could provide large surface area for the cells and proteins to attach. Silk fibrin, adhered onto the surface of hydroxyapatite (HA) crystals, plays a crucial impact on the release profile of selenite ions. The release behavior of the selenite ions exhibited stably slow release fashion. Therefore, it is feasible to employ SF/HASe biocomposites to repair bone defects and apply into the therapy of osteosarcoma postoperatively.