A strategy for challenging tumorous bone regeneration by borosilicate bioactive glass boosting moderate magnetic hyperthermia
Mengke Fan, Chunyu Liu, Yueyao Zhang, Jinlei Zhang, Lu Yang, Kun Su, Pengfei Tian, Yabin Zhou, Liyan Zhang, Xianda Gao, LI Hong-long, Shuaijie Li, Ping Du, Xian Li, Wei Chen, Xu Cui, Haobo Pan
Abstract
Osteosarcoma (OS), with a high tendency for recurrence and metastasis, is associated with severe impairment of bone regeneration. The inherent temperature-sensitive property of tumors positions magnetic hyperthermia (MH) as an increasingly significant area in non-pharmacological cancer treatments. However, the temperature threshold for tumor ablation often causes tissue damage and bone homeostasis imbalance. Therefore, development of moderate MH for OS, capable of achieving tumor ablation while concurrently restoring bone homeostasis, offers significant potential for addressing this challenge. This study integrates magnetothermal nanoparticles with defined temperature thresholds and borosilicate bioactive glass (BSG) to create an injectable magnetothermal bioactive system that allows for regulation of MH temperature. The ionic and alkaline microenvironment from BSG degradation primarily impairs the malignant behavior of OS cells by activating the TNF signaling pathway. This sickening effect diminishes the hyperthermia tolerance of OS cells, thereby boosting apoptosis of OS cells, even in the presence of the limited anti-tumor effects of moderate MH. Furthermore, the combination of moderate MH and BSG also promotes optimal bone formation by stimulating human bone marrow mesenchymal stem cells (hBMSCs) via calcium and JAK-STAT3 signaling pathways. Collectively, this flourishes the therapeutic approaches and theories for the prevention and management of clinically refractory bone tumors. The development of moderate magnetic hyperthermia (MH) for tumor ablation while concurrently restoring bone homeostasis shows potential for osteosarcoma (OS) therapy. Here this group combines magnetothermal nanoparticles with MH temperature-controlled borosilicate bioactive glass achieving OS cell impair while activating TNF signaling pathway for therapeutic purpose.