Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

Abstract

Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. Conclusion The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA

“…However, periodontitis was reported that can suppress the alveolar bone healing via disturbing osteogenic and osteoclastic balance resulting in the loss of teeth [ 30 ]. Macrophages have been reported to be phenotypically plastic and can be activated into reparative M2-like macrophages [ 31 ], which can promote osteoblast differentiation while inhibiting osteoclast formation [ 32 , 33 ]. Therefore, gaining further insights into the mechanisms of reparative M2 macrophages-induced osteoprotective effect will be of great significance for the treatment of periodontitis.…”

Three-Dimensionally Printed Ti2448 With Low Stiffness Enhanced Angiogenesis and Osteogenesis by Regulating Macrophage Polarization via Piezo1/YAP Signaling Axis

“…The plasticity and importance of macrophages in the process of bone repair make them a potential regulatory target for promoting bone repair ( He et al, 2020 ). Some studies have reported that some angiogenic factors are secreted by macrophages ( Ge et al, 2021 ). For example, M1 macrophages can secrete VEGF and promote the germination and extension of blood vessels ( Luo et al, 2021 ).…”

Nanomaterials for Breast Cancer

“…A bioactive multifunctional CePO4/CS/GO scaffold--formed by the combination of graphene oxide (GO) nanoparticles, CePO4 nanobars and bioactive chitosan (CS)--shows characteristics of photothermal therapy in killing tumors, generating macrophage polarization, promoting blood vessels formation, and induction of bone formation. This scaffold may become a promising platform for the treatment of breast cancer bone metastases by destroying residual bone tumor cells after photothermal therapy and subsequent healing of the bone defects (12). Similarly, graphene oxide (GO) nanocomposites, loaded with superparamagnetic iron oxide nanoparticles spliced with polyethylene glycol (PEG) and grafted with methotrexate and stimulus-sensitive linkers (GO-SPION-MTX), have been developed for photothermal and chemotherapy of breast cancer.…”