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

作者全名："Yu, Kexiao; Zhou, Hang; Xu, Yamei; Cao, Youde; Zheng, Yuanyi; Liang, Bing"

作者地址："[Yu, Kexiao] Chongqing Tradit Chinese Med Hosp, Dept Orthoped, 6 Panxi Seventh Branch Rd, Chongqing 400021, Peoples R China; [Zhou, Hang] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Xu, Yamei; Cao, Youde; Liang, Bing] Chongqing Med Univ, Coll Basic Med, Mol Med Diagnost & Testing Ctr, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Zheng, Yuanyi] Shanghai Jiao Tong Univ Affiliated Sixth Peoples H, Shanghai Inst Ultrasound Med, Dept Ultrasound Med, 600 Yishan Rd, Shanghai 200233, Peoples R China; [Zhou, Hang; Liang, Bing] Chongqing Med Univ, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China"

通信作者："Liang, B (通讯作者)，Chongqing Med Univ, Coll Basic Med, Mol Med Diagnost & Testing Ctr, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Zheng, YY (通讯作者)，Shanghai Jiao Tong Univ Affiliated Sixth Peoples H, Shanghai Inst Ultrasound Med, Dept Ultrasound Med, 600 Yishan Rd, Shanghai 200233, Peoples R China.; Liang, B (通讯作者)，Chongqing Med Univ, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China."

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001013755000001

JCR分区：Q1

影响因子：10.6

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

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

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."

基金机构："National Natural Science Foundation of China [82203067, 82102909]; China Postdoctoral Science Foundation [2021M693754]; Chongqing Special Postdoctoral Science Foundation [2021XM2023]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxm2234, CSTB2022NSCQ-MSX0109]"

基金资助正文："AcknowledgementsWe acknowledge financial support from the National Natural Science Foundation of China (Grant Nos. 82203067 and 82102909), the China Postdoctoral Science Foundation (2021M693754), the Chongqing Special Postdoctoral Science Foundation (2021XM2023), and the Natural Science Foundation of Chongqing (Grant Nos. cstc2020jcyj-msxm2234 and CSTB2022NSCQ-MSX0109)."