Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, 200234, China.
J Nanobiotechnology. 2021 Jan 7;19(1):11. doi: 10.1186/s12951-020-00753-9.
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.
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.
Graphene oxide (GO) nanoparticles, hydrated CePO nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO/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 Ce 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 Ce ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration.
The multifunctional CePO/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.
乳腺癌骨转移已成为最常见的并发症之一；然而，它可能导致癌症复发和骨不愈合以及局部骨缺损。
在此，通过 CCK8 试验、活/死细胞染色和流式细胞术，我们在体外验证了生物支架材料对细胞增殖和凋亡的影响。我们使用免疫荧光技术和流式细胞术来验证生物支架材料是否调节巨噬细胞极化，并用碱性磷酸酶（ALP）染色、茜素红染色和 PCR 来验证生物支架材料是否促进骨再生。在体内，我们通过测量小鼠肿瘤体积、Tunel 染色和 caspase-3 免疫荧光再次研究了生物支架材料对肿瘤的影响。我们还构建了小鼠颅骨终极缺损模型来验证其对骨再生的影响。
氧化石墨烯（GO）纳米粒子、水合磷酸铈纳米棒和生物活性壳聚糖（CS）结合形成了一种具有光热治疗以杀死肿瘤、促进血管形成和诱导骨形成的多功能磷酸铈/CS/GO 支架。CePO/CS/GO 支架激活局部肿瘤细胞中的 caspase-3 蛋白酶，从而裂解核小体之间的 DNA 并导致细胞凋亡。一方面，释放的 Ce 离子促进巨噬细胞 M2 极化，巨噬细胞分泌血管内皮生长因子（VEGF）和精氨酸酶-1（Arg-1），从而促进血管生成。另一方面，释放的 Ce 离子还激活了骨形态发生蛋白 2/Smad 信号通路，促进了骨组织的再生。
多功能 CePO/CS/GO 支架可能成为治疗乳腺癌骨转移的有前途的平台。
