Institute of Ultrasound Imaging of Chongqing Medical University, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, PR China; Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, PR China.
Institute of Ultrasound Imaging of Chongqing Medical University, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, PR China.
Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110460. doi: 10.1016/j.msec.2019.110460. Epub 2019 Nov 19.
Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with FeO nanoparticles and the antitumor drug doxorubicin (DOX/FeO@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/FeO@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with FeO nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/FeO@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/FeO@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/FeO@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.
骨髓抑制、胃肠道毒性和过敏反应常伴随骨肉瘤（OS）的化疗。此外，OS 复杂的核型、缺乏靶向抗肿瘤药物以及为肿瘤细胞提供保护腔的骨微环境，降低了化疗的疗效。在此，我们开发了一种载有 FeO 纳米颗粒和抗肿瘤药物阿霉素（DOX/FeO@PMMA）的多功能骨水泥，用于协同 MH 消融和骨肉瘤化疗。局部瘤内给予的 DOX/FeO@PMMA 可通过聚合反应在肿瘤部位从液体变为固体。设计的多功能骨水泥由美国食品和药物管理局（FDA）批准的 FeO 纳米颗粒、PMMA 和抗肿瘤药物组成。详细研究了 DOX/FeO@PMMA 的可注射性、磁热疗（MH）性能、药物控制释放特性以及在体外的协同治疗效果。此外，设计的 DOX/FeO@PMMA 控制 DOX 的释放，增强 OS 组织的细胞凋亡，抑制肿瘤细胞的增殖，在体内表现出协同的 MH 消融和骨肉瘤化疗作用。还详细评估了 DOX/FeO@PMMA 的生物安全性。该策略显著减少了手术时间，避免了手术伤口，减轻了患者的痛苦，为骨肉瘤的治疗提供了巨大的临床转化潜力。
