程亮教授课题组及其合作者在Natl. Sci. Rev.上发表论文

作者：

Zhuorun Song^1,2#, Shunyi Lu^1,2#, Yuqi Yang², Zijun Chen³, Youdong Chen², Jie Cao², Zimin Zhang¹, Jun Ge^1,2*, Huilin Yang¹* and Liang Cheng²*

单位：

¹The First Affiliated Hospital of Soochow University Department of Orthopedic Surgery, Suzhou 215006

²Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123

³Obstetrics & Gynecology Hospital of Fudan University Department of Breast Surgery, Yangtze River Delta Integration Demonstration Zone (Qingpu), Shanghai 201799

摘要：

A metabolic reprogramming strategy, considered an efficient way to enhance current therapies, has provided renewed hope for treating osteosarcoma (OS), which has reached a bottleneck in clinical practice. In this study, SHK@Mn-TiO₂ were developed as novel SDT agents with glycolysis-inhibiting properties. By reducing the expression of PKM2 and HK-2, SHK@Mn-TiO₂ effectively inhibited glycolysis, thereby reversing the hypoxic TME, as evidenced by more than ∼ 50% decrease in HIF-1α and lactate (LA) levels compared with those of Mn-TiO₂. Under this O₂-enriched TME, SHK@Mn-TiO₂ enhanced intracellular reactive oxygen species (ROS) levels by approximately 53% and increased K7M2 tumor inhibition under ultrasound (US). Furthermore, the combination of glycolysis inhibition and SDT initiated a cascade of immune responses, promoting a ∼ 98% increase in the maturation of dendritic cells and a ∼ 280% increase in the infiltration of IFN-γ⁺ CD8⁺ T cells compared with those in the control. The typically immunosuppressive TME induced by conventional SDT was significantly reversed, as indicated by the reduction in the proportions of regulatory T cells to ∼ 18% and myeloid-derived suppressor cells (MDSCs) to ∼ 49% in the Mn-TiO₂ groups. Moreover, a long-term immune memory effect was observed in the K7M2 tumor rechallenge model as a result of strong immune activation. Overall, this study highlights a sono-immune strategy for OS treatment based on the synergistic effects of glycolysis inhibition combined with SDT, offering a promising solution to the current therapeutic challenges in clinical OS management.

影响因子：

17.1

分区情况：

一区

链接：

https://doi.org/10.1093/nsr/nwaf365