Abstract
Objective. To explore the therapeutic effects and mechanism of fluorescent mitoxantrone hydrochloride nanoparticles on giant cell tumor of bone. Methods. The adsorption capacity of nanoparticles to hydroxyapatite (HA), cell adsorption capacity, encapsulation rate, particle size, and potential of the nanoparticles were determined by HPLC and Zetasizer Nano ZS nanomicelle potentiometer. MTT assay was used to determine the toxicity of nanoparticles to cells. The fluorescent intensity of the nanoparticles and their location in the cells were observed under a fluorescence microscope. RT-qPCR and Western blotting were then used to measure the expression levels of miRNA, mRNA, and proteins in cells. Transwell and Annexin V-FITC/PI staining tests were used to study the cell invasion and apoptotic rate, respectively. The dual-luciferase reporter gene experiment was then carried out to verify the binding relationship between miR-125b and its predicted target. Results. ALN-FOL-MTO-NLC nanoparticles showed a stronger adsorption capacity for HA and stronger toxicity to GCTB28 cells. Compared to normal tissues, the expression level of miR-125b in giant bone tumor tissue and cells was significantly downregulated, and the expression level of miR-125b was upregulated to some extent after treatment. Overexpression of miR-125b or treatment of ALN-FOL-MTO-NLC nanoparticles can inhibit the malignant behavior of GCTB28 cells, whereas the inhibition of the expression of miR-125b can promote the malignant behavior of GCTB28 cells. The result showed that parathyroid hormone receptor 1 (PTH1R) was a downstream target gene for miR-125b. Rescue experiment showed that the treatment of GCTB28 with ALN-FOL-MTO-NLC nanoparticles while inhibiting miR-125b expression can reduce the inhibitory effect of miR-125b on the malignant behavior of GCTB28 cells, whereas upregulating the expression levels of miR-125b and PTH1R in GCTB28 cells had no significant effect on the malignant behavior of GCTB28 cells. Conclusion. ALN-FOL-MTO-NLC nanoparticles have a certain inhibitory effect on the malignant behavior of giant cell tumor of bone through the miR-125b/PTH1R molecular axis.
Highlights
Giant cell tumor of bone (GCT) is a bone tumor with high invasiveness and osteolytic nature [1] with potential malignancy [2]
The preferred treatment for GCT is local treatment with assisted surgery, but this treatment has a higher postoperative recurrence rate [4]; it is important to find a new way for GCT treatment
As one of the most common primary bone tumors, GCT is frequently occurred in young people and often happens around the knee joint
Summary
Giant cell tumor of bone (GCT) is a bone tumor with high invasiveness and osteolytic nature [1] with potential malignancy [2]. GCT is mainly composed of three kinds of cells, including bone cell-like multinucleated giant cells, spindlelike stromal cells, and monocytes [3]. Considering the structural characteristics of human tissues, nanoparticles have good advantages in size, can interact with the biological components of the human body, and regulate various biological behaviors of the human body [5]. The nanodrug showed strong permeability, greater solubility, better adsorption, and so on in biology. Due to the small size and large surface area of nanoparticles, nanodrugs are easy to pass
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