2. Academic Validation
  3. D-arginine-loaded metal-organic frameworks nanoparticles sensitize osteosarcoma to radiotherapy

D-arginine-loaded metal-organic frameworks nanoparticles sensitize osteosarcoma to radiotherapy

  • Biomaterials. 2021 Feb:269:120642. doi: 10.1016/j.biomaterials.2020.120642.
Chuanchao Du 1,  Mengxue Zhou 2,  Fei Jia 1,  Lifo Ruan 2,  Huiru Lu 2,  Jiayu Zhang 2,  Bin Zhu 1,  Xiaoguang Liu 3,  Jun Chen 4,  Zhifang Chai 2,  Yi Hu 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, PR China.
  • 2 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.
  • 3 Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, PR China. Electronic address: xgliudoctor@163.com.
  • 4 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. Electronic address: chenjun@ihep.ac.cn.
  • 5 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. Electronic address: huyi@ihep.ac.cn.
PMID: 33440291 DOI: 10.1016/j.biomaterials.2020.120642
Abstract

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.

Keywords

D-arginine; Hypoxia; Metal-organic frameworks; Osteosarcoma; Radiotherapy.

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