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.

中文翻译：

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盐酸米托蒽醌纳米颗粒通过miR-125b / PTH1R轴抑制骨巨细胞瘤的恶性行为

目标。探讨荧光米托蒽醌盐酸盐纳米颗粒对骨巨细胞瘤的治疗作用及其机制。方法。用HPLC和Zetasizer Nano ZS纳米胶束电位计测定纳米颗粒对羟基磷灰石（HA）的吸附能力，细胞吸附能力，包封率，粒径和电势。使用MTT测定法确定纳米颗粒对细胞的毒性。在荧光显微镜下观察纳米颗粒的荧光强度及其在细胞中的位置。然后使用RT-qPCR和Western印迹法测量细胞中miRNA，mRNA和蛋白质的表达水平。Transwell和Annexin V-FITC / PI染色测试分别用于研究细胞侵袭和凋亡率。然后进行了双重荧光素酶报告基因实验，以验证miR-125b与其预测靶标之间的结合关系。结果。ALN-FOL-MTO-NLC纳米颗粒对HA的吸附能力更强，对GCTB28细胞的毒性更强。与正常组织相比，巨大骨肿瘤组织和细胞中miR-125b的表达水平显着下调，治疗后miR-125b的表达水平上调。miR-125b的过表达或ALN-FOL-MTO-NLC纳米粒子的处理可以抑制GCTB28细胞的恶性行为，而抑制miR-125b的表达则可以促进GCTB28细胞的恶性行为。结果表明甲状旁腺激素受体1（PTH1R）是miR-125b的下游靶基因。结论。ALN-FOL-MTO-NLC纳米颗粒通过miR-125b / PTH1R分子轴对骨巨细胞瘤的恶性行为具有一定的抑制作用。