Ma Limin, Zhou Jielong, Wu Qiong, Luo Guowen, Zhao Manzhi, Zhong Guoqing, Zheng Yufeng, Meng Xianwei, Cheng Shi, Zhang Yu
Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
Biomaterials. 2023 Oct;301:122236. doi: 10.1016/j.biomaterials.2023.122236. Epub 2023 Jul 18.
Tumor recurrence and a lack of bone-tissue integration are two critical concerns in the surgical treatment of osteosarcoma. Thus, an advanced multifunctional therapeutic platform capable of simultaneously eliminating residual tumor cells and promoting bone regeneration is urgently needed for efficient osteosarcoma treatment. Herein, to thoroughly eliminate tumors and simultaneously promote bone regeneration, an intelligent multifunctional therapeutic scaffold has been engineered by integrating microwave-responsive zeolitic imidazolate framework 8 (ZIF-8) nanomaterials loaded with a chemotherapeutic drug and an immune checkpoint inhibitor onto 3D-printed titanium scaffolds. The constructed scaffold features distinct microwave-thermal sensitization and tumor microenvironment-responsive characteristics, which can induce tumor immunogenic death by microwave hyperthermia and chemotherapy. Orthotopic implantation of the nanocomposite scaffold results in an enhanced immune response against osteosarcoma that may effectively inhibit tumor recurrence through synergistic immunotherapy. During long-term implantation, the zinc ions released from the degradation of ZIF-8 can induce the osteogenic differentiation of stem cells. The porous structure and mechanical properties of the 3D-printed titanium scaffolds provide a structural microenvironment for bone regeneration. This study provides a paradigm for the design of multifunctional microwave-responsive composite scaffolds for use as a therapy for osteosarcoma, which could lead to improved strategies for the treatment of the disease.
肿瘤复发和骨组织整合不足是骨肉瘤外科治疗中的两个关键问题。因此，迫切需要一种先进的多功能治疗平台，能够同时消除残留肿瘤细胞并促进骨再生，以实现骨肉瘤的有效治疗。在此，为了彻底消除肿瘤并同时促进骨再生，通过将负载化疗药物和免疫检查点抑制剂的微波响应性沸石咪唑酯骨架8（ZIF-8）纳米材料整合到3D打印钛支架上，构建了一种智能多功能治疗支架。所构建的支架具有独特的微波热敏化和肿瘤微环境响应特性，可通过微波热疗和化疗诱导肿瘤免疫原性死亡。纳米复合支架的原位植入导致针对骨肉瘤的免疫反应增强，可能通过协同免疫疗法有效抑制肿瘤复发。在长期植入过程中，ZIF-8降解释放的锌离子可诱导干细胞的成骨分化。3D打印钛支架的多孔结构和力学性能为骨再生提供了结构微环境。本研究为设计用于骨肉瘤治疗的多功能微波响应复合支架提供了范例，这可能会带来该疾病治疗的改进策略。
