Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present...Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.展开更多
基金funded by National Key Research and Development Program of China(Grant No.2018YFC1106302 and 2018YFA0703100)National Natural Science Foundation of China(Grant No.51772210,U2001221,51802340,81871774 and 82072422)+1 种基金Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)Shenzhen Fundamental Research Foundation(Grant No.JCYJ20200109114620793).
文摘Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.
