Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment.
Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment.
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成骨和抗肿瘤铜锰掺杂硼硅酸盐纳米颗粒用于骨肿瘤治疗中的综合骨修复和化学动力学治疗
DOI：
10.1016/j.bioactmat.2021.10.030
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发表时间：
2022-06
影响因子：
18.9
通讯作者：
Pan H
中科院分区：
文献类型：
--
作者：
Pang L;Zhao R;Chen J;Ding J;Chen X;Chai W;Cui X;Li X;Wang D;Pan H
恶性骨肿瘤广泛切除后引起的严重骨缺损和残留肿瘤细胞引起的肿瘤复发的可能性使恶性骨肿瘤的治疗成为一个重大的临床挑战。目前的治疗策略集中于植入骨替代物以填充缺损，但在增强骨再生和抑制肿瘤细胞生长方面均失败。因此，Cu、Mn掺杂的硼硅酸盐纳米颗粒（BSNs）可用于骨修复和抗肿瘤治疗，其可通过Cu2+和Mn3+的成骨作用促进骨再生，同时通过Cu2+和Mn3+的类Fenton反应产生的羟基自由基诱导肿瘤细胞凋亡。体外实验表明BSNs能促进BMSCs的成骨分化和内皮细胞的血管生成，体内实验表明BSNs能有效修复大鼠严重骨缺损。同时，BSNs在模拟肿瘤微环境中可通过类Fenton反应产生羟自由基，促进细胞内活性氧的产生，最终诱导肿瘤细胞凋亡。BSN对小鼠皮下肿瘤有较好的抑制作用，对正常组织器官无毒副作用。总之，本工作中开发的Cu和Mn掺杂的BSN具有促进骨生成和血管生成以促进骨再生和抑制肿瘤生长以进行化学动力学治疗的双重功能，因此具有融合骨修复和抗肿瘤治疗的巨大潜力。成功合成了具有生物活性的双功能硼硅酸盐纳米粒子。将Cu和Mn掺入纳米颗粒增强了骨生成和血管生成。Cu、Mn掺杂的硼硅酸盐纳米粒子通过产生·OH抑制肿瘤生长。骨肿瘤治疗中骨修复和化学动力学疗法的潜在融合。
Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge. The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells. Herein, Cu and Mn-doped borosilicate nanoparticles (BSNs) were developed for syncretic bone repairing and anti-tumor treatment, which can enhance bone regeneration through the osteogenic effects of Cu2+ and Mn3+ ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu2+ and Mn3+ ions. In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs, and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation. Meanwhile, BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment, promote the generation of intracellular reactive oxygen species, and eventually induce tumor cell apoptosis. Besides, subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs. Altogether, Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration, and inhibiting tumor growth for chemodynamic therapy, thus holding a great potential for syncretic bone repairing and anti-tumor therapy. Dual-functional bioactive borosilicate nanoparticles were successfully synthesized. Incorporation of Cu and Mn to the nanoparticles enhanced osteogenesis and angiogenesis. Cu and Mn doped borosilicate nanoparticles inhibited tumor by producing ·OH. Potential syncretic bone repair and chemodynamic therapy developed for bone tumor treatment.
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