Orchestrated tumor apoptosis (Cu2+) and bone tissue calcification (Ca2+) by hierarchical Copper/Calcium-ensembled bioactive silica for osteosarcoma therapy.

[Display omitted] • Cu species are optimally impregnated along with Ca species in BG networks. • Cu-BG without drug induced Fenton-like reaction-assisted deadly free radicals. • Ca species in BG presented enhanced calcification for osteogenesis. • Biocompatible Cu-BG networks enhanced the (HIF)-1α expression. • Cu-BG networks showed synergistic cancer killing and bone regeneration abilities. Malignant osteosarcoma is one of the serious health concerns attributed to inferior prognosis and uncontrolled metastasis in clinics. Indeed, multifunctional therapeutics with precise tumor killing and subsequent regeneration of damaged tissue are of immense requirement in treating osteosarcoma. Herein, this study demonstrates the fabrication of versatile calcium/copper-impregnated bioactive glass (Ca-BG/Cu-BG) frameworks with orchestrated cancer inhibition and bone tissue calcification towards osteosarcoma therapy. Initially, the designed composites are systematically characterized to explore various morphological attributes and physicochemical properties. The optimal formulation of Cu-BG (10 mol%) presented orchestrated effects of an excellent pH-responsive anticancer effect through hydroxyl radical (·OH) generation and facilitated hydroxyapatite formation towards bone tissue calcification. Further , in vitro investigations demonstrated substantial biocompatibility in mouse embryo osteoblast precursor cell line (MC3T3-E1) and exceptional anti-tumor effects in human osteosarcoma cells (HOS) through improved cellular internalization efficacy and free radical generation, respectively. Finally, in vivo immunostaining and micro-computed tomography (μCT) images of osteosarcoma-bearing mice confirmed Fenton-like reaction-induced chemodynamic therapy (CDT), over-expressed hypoxia-inducible factor (HIF)-1α through p53 pathway, and formation of calcified nodules. In addition, hematological analyses of hematoxylin-eosin (HE) stained main organ sections presented biosafety elucidations. Together, the synergistic prospects of Cu2+ and Ca2+ species had substantially orchestrated towards regenerative medicine. [ABSTRACT FROM AUTHOR]