Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, PR China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China.
Biomaterials. 2021 Feb;269:120642. doi: 10.1016/j.biomaterials.2020.120642. Epub 2021 Jan 2.
Osteosarcoma is a common type of bone cancers with a high rate of pulmonary recurrence. High-dose radiation therapy is useful for the ablation of unresectable osteosarcoma. However, it may cause severe adverse effects. To address this problem, we developed D-arginine-loaded metal-organic frameworks (MOF) nanoparticles for improving the radiosensitivity of osteosarcoma. D-arginine, a metabolically inert enantiomer of L-arginine, could produce nitric oxide and down-regulate hypoxia-inducible factor-1alpha (HIF-1α) to alleviate tumor hypoxia. In addition, MOF could also generate free radicals to kill the tumor cells. Results demonstrate that D-arginine-loaded nanoparticles enhanced tumor ablation and prevented the lung metastasis in mice upon radiation therapy. Furthermore, the nanoparticles or radiation alone had relatively low toxicity in cells and mice. Therefore, D-arginine-loaded MOF nanoparticles are relatively safe and highly effective in sensitizing osteosarcoma to radiotherapy.
骨肉瘤是一种常见的骨癌，其肺部复发率较高。高剂量辐射治疗对不可切除的骨肉瘤消融有效。然而，它可能会引起严重的不良反应。为了解决这个问题，我们开发了负载 D-精氨酸的金属有机骨架（MOF）纳米颗粒，以提高骨肉瘤的放射敏感性。D-精氨酸是 L-精氨酸的代谢惰性对映体，可产生一氧化氮并下调缺氧诱导因子-1α（HIF-1α），从而减轻肿瘤缺氧。此外，MOF 还可以产生自由基杀死肿瘤细胞。结果表明，负载 D-精氨酸的纳米颗粒增强了肿瘤消融，并在放射治疗后预防了小鼠的肺转移。此外，纳米颗粒或单独的辐射在细胞和小鼠中具有相对较低的毒性。因此，负载 D-精氨酸的 MOF 纳米颗粒在提高骨肉瘤放射敏感性方面具有相对安全性和高效性。
