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可注射磁性水凝胶填充剂用于协同骨肿瘤热化疗。

Injectable Magnetic Hydrogel Filler for Synergistic Bone Tumor Hyperthermia Chemotherapy.

机构信息

School of Clinical Medicine, Tsinghua University, Beijing 100084, China.

Department of Orthopedics, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 100084, China.

出版信息

ACS Appl Bio Mater. 2024 Mar 18;7(3):1569-1578. doi: 10.1021/acsabm.3c01074. Epub 2024 Feb 13.


DOI:10.1021/acsabm.3c01074
PMID:38349029
Abstract

The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases.

摘要

骨肿瘤治疗的疗效主要受到肿瘤切除不彻底的限制,导致肿瘤复发和转移,而且肿瘤位置较深。在此,开发了一种可注射的载多柔比星(DOX)的磁性海藻酸钠水凝胶(DOX@MAH),以评估交变磁场(AMF)响应的化学-热协同治疗在骨肿瘤多模式治疗中的疗效。所制备的水凝胶具有优异的载药能力和持续的 DOX 释放。这种多功能性归因于 DOX 用于化学治疗以及含氧化铁纳米粒子的海藻酸钠水凝胶作为磁热疗剂的联合使用,可产生热疗以消除肿瘤,而不受穿透深度的限制。此外,水凝胶与组织中丰富的钙离子接触时会形成凝胶;因此,这种水凝胶可以完美贴合因骨肿瘤组织切除而产生的骨缺损,并且水凝胶可以紧密贴合骨骼的手术边缘,实现化学-热协同治疗的高效残留肿瘤组织消除。水凝胶表现出优异的热疗性能,这可以通过对肿瘤细胞的细胞毒性测试得到证明。这些测试表明,与单一的磁热疗或化学疗法相比,基于 DOX@MAH 的 AMF 联合治疗显著诱导细胞死亡。荷瘤小鼠的抗肿瘤效果表明,在肿瘤部位注射 DOX@MAH 可有效抑制肿瘤生长并导致肿瘤坏死。这项工作不仅建立了有效的 DOX@MAH 系统作为治疗骨肿瘤的协同化学-热疗平台,而且还揭示了海藻酸盐在结合骨骼钙离子治疗骨缺损疾病中的应用。

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[2]
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[3]
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[4]
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