Engineering a triple-functional magnetic gel driving mutually-synergistic mild hyperthermia-starvation therapy for osteosarcoma treatment and augmented bone regeneration

• Published in: Journal of nanobiotechnology 2023-06, Vol.21 (1), p.201-201, Article 201
• Main Authors: Yu, Kexiao, Zhou, Hang, Xu, Yamei, Cao, Youde, Zheng, Yuanyi, Liang, Bing
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Animals; ATP; B cells; Biological activity; Biomedical materials; Bone cancer; Bone growth; Bone healing; Bone Neoplasms - metabolism; Bone Neoplasms - therapy; Bone Regeneration; Bone tumors; Care and treatment; Cell Line, Tumor; Chemotherapy; Comparative analysis; Complications and side effects; Defects; Diagnosis; Differentiation (biology); Fever; Fractures; Glucose; Glucose oxidase; Health aspects; Heat resistance; Heat shock proteins; Heat-Shock Proteins - metabolism; Hydrogels; Hyperthermia; Hyperthermia, Induced; Hypoxia; Iron oxides; Magnesium; Magnesium carbonate; Magnetic Phenomena; Mice; Microenvironments; Mild hyperthermia therapy; Nanoparticles; Osteogenesis; Osteosarcoma; Osteosarcoma - metabolism; Osteosarcoma - therapy; Oxidases; Patient outcomes; Phase transitions; Polylactide-co-glycolide; Rabbits; Radiation therapy; Regeneration; Regeneration (physiology); Sarcoma; Solid phases; Starvation; Starvation therapy; Temperature; Temperature effects; Therapy; Thermomagnetic effects; Thermotherapy; Tissue engineering; Triple-functional magnetic hydrogels; Tumor cells; Tumor Microenvironment; Tumors
• ISSN: 1477-3155; 1477-3155
• 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 (Fe O /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.