Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Seventh Branch Road, Jiangbei District, Chongqing, 400021, P. R. China.
Department of Orthopedics, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong Distinct, Chongqing, 400010, P. R. China.
J Nanobiotechnology. 2023 Jun 26;21(1):201. doi: 10.1186/s12951-023-01955-7.
Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (FeO/GOx/MgCO@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.
恶性骨肿瘤导致高残疾率和死亡率,并且在杀伤肿瘤和修复骨缺损方面都难以治疗。与其他热疗策略相比,由于没有深度限制,磁热疗已成为治疗恶性骨肿瘤的有效疗法。然而,肿瘤细胞表达热休克蛋白(HSP)以抵抗热疗,从而降低了其疗效。竞争型 ATP 消耗可减少 HSP 的产生;幸运的是,葡萄糖氧化酶(GOx)饥饿疗法的基本原理是消耗葡萄糖来控制 ATP 的产生,从而限制 HSP 的产生。我们开发了一种三重功能的磁性凝胶(FeO/GOx/MgCO@PLGA)作为具有固-液相转变能力的磁性骨修复水凝胶(MBRs),以驱动磁热效应,同时触发 GOx 释放并抑制 ATP 产生,减少 HSP 表达,从而实现骨肉瘤协同治疗。此外,磁热疗改善了饥饿疗法对缺氧微环境的作用,实现了相互增强的治疗效果。我们进一步证明了原位 MBRs 注射可有效抑制 143B 骨肉瘤荷瘤小鼠和兔胫骨平台原位骨肿瘤模型中的肿瘤生长。更重要的是,我们的研究还表明,液态 MBRs 可以通过镁离子释放和增强成骨分化来有效匹配骨缺损并加速其重建,从而增强因骨肿瘤引起的骨缺损的再生,为恶性骨肿瘤治疗和骨缺损修复加速提供了新的思路。