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

Journal of Nanobiotechnology

Research

Kexiao Yu¹  Hang Zhou²  Yamei Xu³  Youde Cao³  Bing Liang⁴  Yuanyi Zheng⁵ 

[1] Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Seventh Branch Road, Jiangbei District, 400021, Chongqing, P. R. China;Department of Orthopedics, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong Distinct, 400010, Chongqing, P. R. China;State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, Chongqing Medical University, 400010, Chongqing, People’s Republic of China;Department of Pathology, College of Basic Medicine, Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, 400016, Chongqing, P.R. China;Department of Pathology, College of Basic Medicine, Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, 400016, Chongqing, P.R. China;State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, Chongqing Medical University, 400010, Chongqing, People’s Republic of China;Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Xuhui Distinct, 200233, Shanghai, P. R. China;

关键词: Triple-functional magnetic hydrogels;    Mild hyperthermia therapy;    Starvation therapy;    Osteosarcoma;    Bone regeneration;   

DOI  :  10.1186/s12951-023-01955-7

 received in 2023-04-03, accepted in 2023-06-05,  发布年份 2023

来源: Springer

【 摘 要 】

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 (Fe3O4/GOx/MgCO3@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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2023_37_Article_IEq196.gif

Fig.1

41116_2023_37_Article_IEq83.gif

41116_2023_37_Article_IEq52.gif

41116_2023_37_Article_IEq43.gif

41116_2023_37_Article_IEq22.gif

Fig. 2

Scheme 1