Recently,the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ.This study is focused on the design of a new theragen...Recently,the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ.This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant(Pluronic F127),bioactive glass(BG),and black phosphorus(BP).The nanocomposite was prepared through a two-step synthetic strategy,including a microwave treatment that turned BP nanosheets(BPNS)into quantum dots(BPQDs)with 5±2 nm dimensions in situ.The effects of surfactant and microwave treatment were assessed in vitro:the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite.The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid.The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro,finding that 150μg mL^(-1)was the lowest concentration which prevented the proliferation of SAOS-2 cells,while the counterpart without BP did not affect the cell growth rate.Moreover,the apoptosis pathways were evaluated and a mechanism of action was proposed.NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia.The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer,breast cancer,and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers.The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells;the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells.This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.展开更多
基金support from Progetto MIUR PRIN2017-ACTION,Grant No.2017SZ5WZB and POR Campania FESR 2014-2020(Campania imaging Infrastructure for Research in Oncology-C.I.R.O)The authors also thank Maria Rosaria Bonetti for lab technical support,Cristina Del Barone for facilitating microscopy analysis,Dr.Antonio Pennetta for ICP analysis and Dr.Roberta Marzella for support to project management.CISUP(Centre for Instrument Sharing-University of Pisa)and the EUroBioImaging(EUBI)Facility at CNR(Naples)are acknowledged for the use of the Bruker Avance NEO 500 Solid State NMR spectrometer and of AxioVision microscope(Carl Zeiss Micro Imaging GmbH),respectively.
文摘Recently,the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ.This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant(Pluronic F127),bioactive glass(BG),and black phosphorus(BP).The nanocomposite was prepared through a two-step synthetic strategy,including a microwave treatment that turned BP nanosheets(BPNS)into quantum dots(BPQDs)with 5±2 nm dimensions in situ.The effects of surfactant and microwave treatment were assessed in vitro:the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite.The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid.The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro,finding that 150μg mL^(-1)was the lowest concentration which prevented the proliferation of SAOS-2 cells,while the counterpart without BP did not affect the cell growth rate.Moreover,the apoptosis pathways were evaluated and a mechanism of action was proposed.NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia.The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer,breast cancer,and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers.The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells;the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells.This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.
