Bone tumor is one of major challenging issues clinically. After surgical intervention, a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe nanocrystals (BG-CFS) by combining 3D printing technique with solvothermal method. During the solvothermal reaction process, CuFeSe nanocrystals could in situ grow on the strut surface of BG scaffolds and thus endow BG scaffolds excellent photothermal performance. The photothermal performance of BG-CFS scaffolds could be well regulated through altering the content of CuFeSe nanocrystals and laser power density when exposed to the near infrared laser (808 nm). The BG-CFS scaffolds could not only effectively ablate the bone tumor cells (Saos-2 cells) in vitro, but also significantly inhibit bone tumor growth in vivo. Moreover, BG-CFS scaffolds could stimulate osteogenic gene expressions of rabbit bone marrow stromal cells (rBMSCs) and finally facilitate the formation of new bone in the bone defects. Our study, for the first time, combined the photothermal performance of semiconductor CuFeSe nanocrystals with the bone-forming activity of bioactive glass scaffolds, which can offer a more extensive horizon for developing novel biomaterials with dual functions of bone tumor therapy and bone regeneration.
Nanostructures based on metal-organic frameworks (MOFs) have promising potential as theragnostic nanoplatforms for phototherapy of cancer cells. However, the MOFs alone are seldom reported to be used as photothermal agents mainly due to their poor near-infrared (NIR) light absorption.Methods: Ultrathin copper-tetrakis (4-carboxyphenyl) porphyrin (Cu-TCPP) MOF nanosheets were prepared by a facile solvothermal route. The photothermal therapy (PTT), photodynamic therapy (PDT), and T1-weighted magnetic resonance (MR) imaging capabilities and the high biocompatibility of these composite nanosheets were evaluated in vitro as well as in vivo in a mouse tumor model.Results: The ultrathin Cu-TCPP MOF nanosheets exhibited 1) strong NIR absorption because of the d-d energy band transition of Cu2+ and the ultrathin characteristic translating into excellent photothermal performance, 2) ability to produce singlet oxygen because of the inherent characteristic of TCPP, and 3) capability for MR imaging because of the unpaired 3d electrons of copper.Conclusion: Our study demonstrated that the Cu-TCPP MOF nanosheets are a promising phototherapy nanoplatform with the synergistic ability for PTT and PDT of cancer, guided by MR and infrared thermal imaging.
After surgical resection for a bone tumor, the uncleared bone tumor cells can multiply and cause recurrence of the bone tumor. It is worthwhile to design a scaffold that kills the remaining bone tumor cells and repairs bone defects that were given rise to by surgical resection. Additionally, it is extremely important to consider the function of angiogenesis in the process of bone regeneration because the newly formed blood vessels can offer the nutrients for bone regeneration. In this work, a novel metalorganic framework Cu-TCPP nanosheets interface-structured β-tricalcium phosphate (TCP) (Cu-TCPP-TCP) scaffold was successfully prepared through integrating a 3D-printing technique with an in-situ growth method in a solvothermal system. Owing to the excellent photothermal effect of Cu-TCPP nanosheets, Cu-TCPP-TCP scaffolds that were illuminated by near-infrared (NIR) light demonstrated photothermal performance, which was well regulated through varying the contents of Cu-TCPP nanosheets, and the ambient humidity and power density of NIR light. When cultured with osteosarcoma cells, Cu-TCPP-TCP scaffolds killed a significant quantity of osteosarcoma cells through released heat energy after exposure to NIR light with power density 1.0 W cm −2 and duration 10 min. Similarly, Cu-TCPP-TCP scaffolds ablated subcutaneous bone tumor tissues on the backs of naked mice and suppressed their growth because of the heat energy transformed from NIR light. Invitro studies found that Cu-TCPP-TCP scaffolds ably supported the attachments of both human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs), and significantly stimulated expressions of osteogenesis differentiation-related genes in HBMSCs and angiogenesis differentiation-related genes in HUVECs. After implanting Cu-TCPP-TCP scaffolds into the bone defects of rabbits, they effectively promoted bone regeneration. Thus, the integration of the bone-forming bioactivity of TCP scaffolds with the photothermal properties of Cu-TCPP nanosheets and angiogenesis activity of Cu ions makes Cu-TCPP-TCP scaffolds multifunctional, representing a new horizon to develop biomaterials for simultaneously curing bone tumors and repairing bone defects.
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